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Life is a non-equilibrium state and maintaining it thus requires a constant supply of external energy. To this end, organisms consume nutrients and convert the chemical energy into the universal energy carrier ATP. The energy conversion is achieved by the respiratory chain, which comprises multiple membrane-bound enzymes that convert the chemical energy into an electrochemical proton gradient, which is stored across a biological membrane. This proton gradient is, in turn, consumed by ATP synthase to produce ATP. On a molecular level, this is realized by a series of charge transfer processes, which are catalyzed by the respiratory chain complexes I-IV. These enzymes can also combine into larger assemblies, so-called supercomplexes, although their functional role remains highly debated. In this thesis I will discuss the function of complexes I, III, and IV as well as the mycobacterial III2IV2 obligate supercomplex and the superoxide scavenger superoxide oxidase. To elucidate key functional aspects of these enzymes we have employed computational methods together with structural data and experimental measurements. Specifically, we have investigated the mechanism of complex I deactivation, as well as the proton transfer mechanics in its membrane domain. In complex IV, we have identified a mechanism by which steroid molecules can inhibit the enzyme, and describe how electric fields can selectively direct protons along specific pathways. Moreover, we have explored long-range charge transfer mechanisms in the unique mycobacterial III2IV2 supercomplex, and investigated the mechanism of the unique, membrane-bound superoxide scavenger superoxide oxidase. The combined results shed light on the molecular mechanisms that enable these enzymes to transduce energy.

Life is a non-equilibrium state and maintaining it thus requires a constant supply of external energy. To this end, organisms consume nutrients and convert the chemical energy into the universal energy carrier ATP. The energy conversion is achieved by the respiratory chain, which comprises multiple membrane-bound enzymes that convert the chemical energy into an electrochemical proton gradient, which is stored across a biological membrane. This proton gradient is, in turn, consumed by ATP synthase to produce ATP. On a molecular level, this is realized by a series of charge transfer processes, which are catalyzed by the respiratory chain complexes I-IV. These enzymes can also combine into larger assemblies, so-called supercomplexes, although their functional role remains highly debated. In this thesis I will discuss the function of complexes I, III, and IV as well as the mycobacterial III2IV2 obligate supercomplex and the superoxide scavenger superoxide oxidase. To elucidate key functional aspects of these enzymes we have employed computational methods together with structural data and experimental measurements. Specifically, we have investigated the mechanism of complex I deactivation, as well as the proton transfer mechanics in its membrane domain. In complex IV, we have identified a mechanism by which steroid molecules can inhibit the enzyme, and describe how electric fields can selectively direct protons along specific pathways. Moreover, we have explored long-range charge transfer mechanisms in the unique mycobacterial III2IV2 supercomplex, and investigated the mechanism of the unique, membrane-bound superoxide scavenger superoxide oxidase. The combined results shed light on the molecular mechanisms that enable these enzymes to transduce energy.

Strong coupling of organic molecules to the vacuum field of a nanoscale cavity can be used to modify their chemical and physical properties. We extend the Tavis–Cummings model for molecular ensembles and show that the often neglected interaction terms arising from the static dipole moment and the dipole self-energy are essential for a correct description of the light–matter interaction in polaritonic chemistry. On the basis of a full quantum description, we simulate the excited-state dynamics and spectroscopy of MgH+ molecules resonantly coupled to an optical cavity. We show that the inclusion of static dipole moments and the dipole self-energy is necessary to obtain a consistent model. We construct an efficient two-level system approach that reproduces the main features of the real molecular system and may be used to simulate larger molecular ensembles.

Strong coupling of organic molecules to the vacuum field of a nanoscale cavity can be used to modify their chemical and physical properties. We extend the Tavis–Cummings model for molecular ensembles and show that the often neglected interaction terms arising from the static dipole moment and the dipole self-energy are essential for a correct description of the light–matter interaction in polaritonic chemistry. On the basis of a full quantum description, we simulate the excited-state dynamics and spectroscopy of MgH+ molecules resonantly coupled to an optical cavity. We show that the inclusion of static dipole moments and the dipole self-energy is necessary to obtain a consistent model. We construct an efficient two-level system approach that reproduces the main features of the real molecular system and may be used to simulate larger molecular ensembles.

Strong coupling of organic molecules to the vacuum field of a nanoscale cavity can be used to modify their chemical and physical properties. We extend the Tavis–Cummings model for molecular ensembles and show that the often neglected interaction terms arising from the static dipole moment and the dipole self-energy are essential for a correct description of the light–matter interaction in polaritonic chemistry. On the basis of a full quantum description, we simulate the excited-state dynamics and spectroscopy of MgH+ molecules resonantly coupled to an optical cavity. We show that the inclusion of static dipole moments and the dipole self-energy is necessary to obtain a consistent model. We construct an efficient two-level system approach that reproduces the main features of the real molecular system and may be used to simulate larger molecular ensembles.

Life is a non-equilibrium state and maintaining it thus requires a constant supply of external energy. To this end, organisms consume nutrients and convert the chemical energy into the universal energy carrier ATP. The energy conversion is achieved by the respiratory chain, which comprises multiple membrane-bound enzymes that convert the chemical energy into an electrochemical proton gradient, which is stored across a biological membrane. This proton gradient is, in turn, consumed by ATP synthase to produce ATP. On a molecular level, this is realized by a series of charge transfer processes, which are catalyzed by the respiratory chain complexes I-IV. These enzymes can also combine into larger assemblies, so-called supercomplexes, although their functional role remains highly debated. In this thesis I will discuss the function of complexes I, III, and IV as well as the mycobacterial III2IV2 obligate supercomplex and the superoxide scavenger superoxide oxidase. To elucidate key functional aspects of these enzymes we have employed computational methods together with structural data and experimental measurements. Specifically, we have investigated the mechanism of complex I deactivation, as well as the proton transfer mechanics in its membrane domain. In complex IV, we have identified a mechanism by which steroid molecules can inhibit the enzyme, and describe how electric fields can selectively direct protons along specific pathways. Moreover, we have explored long-range charge transfer mechanisms in the unique mycobacterial III2IV2 supercomplex, and investigated the mechanism of the unique, membrane-bound superoxide scavenger superoxide oxidase. The combined results shed light on the molecular mechanisms that enable these enzymes to transduce energy.

Strong coupling of organic molecules to the vacuum field of a nanoscale cavity can be used to modify their chemical and physical properties. We extend the Tavis–Cummings model for molecular ensembles and show that the often neglected interaction terms arising from the static dipole moment and the dipole self-energy are essential for a correct description of the light–matter interaction in polaritonic chemistry. On the basis of a full quantum description, we simulate the excited-state dynamics and spectroscopy of MgH+ molecules resonantly coupled to an optical cavity. We show that the inclusion of static dipole moments and the dipole self-energy is necessary to obtain a consistent model. We construct an efficient two-level system approach that reproduces the main features of the real molecular system and may be used to simulate larger molecular ensembles.

The series of metal–organic frameworks M-MOF-74 gained popularity in the field of capture and separation of CO2 due to the presence of numerous, highly reactive open-metal sites. The description of effective interactions between guest molecules and open-metal sites without accounting for polarization effects is challenging but it can significantly reduce the computational cost of simulations. In this study, we propose a non-polarizable force field for CO2, and H2 adsorption in M-MOF-74 (M = Ni, Cu, Co, Fe, Mn, Zn) by scaling the Coulombic interactions of M-MOF-74 atoms, and Lennard-Jones interaction potentials between the center of mass of H2 and the open-metal centers. The presented force field is based on UFF and DREIDING parameters, characterized by high transferability and efficiency. The quantum behavior of H2 at cryogenic temperatures is considered by incorporating Feynman–Hibbs quantum corrections. To validate the force field, the experimental isotherms of CO2 at 298 K and 10−1 – 102kPa, the isotherms of H2 at 77 K and 10−5 – 102kPa, the corresponding enthalpy of adsorption, and the binding geometries in the M-MOF-74 series were reproduced using Monte Carlo simulations in the grand-canonical ensemble. The computed loadings, heats of CO2 and H2 adsorption, and binding geometries in M-MOF-74 are in very good agreement with the experimental values. The temperature transferability of the force field from 77 K to 87 K, and 298 K was shown for adsorption of H2. The validated force field was used to study the adsorption and separation of CO2/H2 mixtures at 298 K. The adsorption of H2 practically does not occur when CO2 is present in the mixture. As indicated from simulated breakthrough curves, the breakthrough time of CO2 in M-MOF-74 follows the same order a, Engineering Thermodynamics

The series of metal–organic frameworks M-MOF-74 gained popularity in the field of capture and separation of CO2 due to the presence of numerous, highly reactive open-metal sites. The description of effective interactions between guest molecules and open-metal sites without accounting for polarization effects is challenging but it can significantly reduce the computational cost of simulations. In this study, we propose a non-polarizable force field for CO2, and H2 adsorption in M-MOF-74 (M = Ni, Cu, Co, Fe, Mn, Zn) by scaling the Coulombic interactions of M-MOF-74 atoms, and Lennard-Jones interaction potentials between the center of mass of H2 and the open-metal centers. The presented force field is based on UFF and DREIDING parameters, characterized by high transferability and efficiency. The quantum behavior of H2 at cryogenic temperatures is considered by incorporating Feynman–Hibbs quantum corrections. To validate the force field, the experimental isotherms of CO2 at 298 K and 10−1 – 102kPa, the isotherms of H2 at 77 K and 10−5 – 102kPa, the corresponding enthalpy of adsorption, and the binding geometries in the M-MOF-74 series were reproduced using Monte Carlo simulations in the grand-canonical ensemble. The computed loadings, heats of CO2 and H2 adsorption, and binding geometries in M-MOF-74 are in very good agreement with the experimental values. The temperature transferability of the force field from 77 K to 87 K, and 298 K was shown for adsorption of H2. The validated force field was used to study the adsorption and separation of CO2/H2 mixtures at 298 K. The adsorption of H2 practically does not occur when CO2 is present in the mixture. As indicated from simulated breakthrough curves, the breakthrough time of CO2 in M-MOF-74 follows the same order a

Exascale computing has been a dream for ages and is close to becoming a reality that will impact how molecular simulations are being performed, as well as the quantity and quality of the information derived for them. We review how the biomolecular simulations field is anticipating these new architectures, making emphasis on recent work from groups in the BioExcel Center of Excellence for High Performance Computing. We exemplified the power of these simulation strategies with the work done by the HPC simulation community to fight Covid-19 pandemics.

Exascale computing has been a dream for ages and is close to becoming a reality that will impact how molecular simulations are being performed, as well as the quantity and quality of the information derived for them. We review how the biomolecular simulations field is anticipating these new architectures, making emphasis on recent work from groups in the BioExcel Center of Excellence for High Performance Computing. We exemplified the power of these simulation strategies with the work done by the HPC simulation community to fight Covid-19 pandemics. This article is categorized under: Data Science > Computer Algorithms and Programming Data Science > Databases and Expert Systems Molecular and Statistical Mechanics > Molecular Dynamics and Monte-Carlo Methods., QC 20230227

The foundation of all life is the interaction of molecules. Molecular interaction occurs in the tightly packed cytoplasm. In this crowded environment, the molecules need to be able to establish stable interactions with specific interaction partners, and with specific ones only. Selectivity is essential for transcriptional regulation where DNA-binding proteins, more specifically transcription factors, need to reach their respective target DNA, such as an operator sequence, quickly. The transcription factor LacI for example reaches its DNA operator within minutes and establishes a tight interaction to it that will block transcriptions of the genes it regulates. With the other millions of sequences in the bacterial chromosome, it interacts only fleetingly. This is possible because a small part of the protein is disordered during the transient interaction with non-operator DNA. Only with specific DNA will the folding of the disordered region into a rigid helix be favored. When the disordered region folds into a helix, the transcription factor changes its structure and, with it, its function from a weak DNA binder to a strong one. Thinking about molecular structures as dynamic entities that react to their environment and understanding the origins of structural metamorphosis allow us to predict changes in the protein sequence that will affect their behavior in the cellular context. This is demonstrated in this thesis where I study the structural dynamics of LacI with molecular dynamic simulations and use the insights from these simulations to design protein variants with changed binding stability and selectivity.

The foundation of all life is the interaction of molecules. Molecular interaction occurs in the tightly packed cytoplasm. In this crowded environment, the molecules need to be able to establish stable interactions with specific interaction partners, and with specific ones only. Selectivity is essential for transcriptional regulation where DNA-binding proteins, more specifically transcription factors, need to reach their respective target DNA, such as an operator sequence, quickly. The transcription factor LacI for example reaches its DNA operator within minutes and establishes a tight interaction to it that will block transcriptions of the genes it regulates. With the other millions of sequences in the bacterial chromosome, it interacts only fleetingly. This is possible because a small part of the protein is disordered during the transient interaction with non-operator DNA. Only with specific DNA will the folding of the disordered region into a rigid helix be favored. When the disordered region folds into a helix, the transcription factor changes its structure and, with it, its function from a weak DNA binder to a strong one. Thinking about molecular structures as dynamic entities that react to their environment and understanding the origins of structural metamorphosis allow us to predict changes in the protein sequence that will affect their behavior in the cellular context. This is demonstrated in this thesis where I study the structural dynamics of LacI with molecular dynamic simulations and use the insights from these simulations to design protein variants with changed binding stability and selectivity.

Formic acid production from CO2 allows the reduction of carbon dioxide emissions while synthesizing a product with a wide range of applications. CO2 hydrogenation is challenging due to the cost of transition metal catalysts and the toxicity of the transition elements. In this work, the thermodynamic confinement effects of the metal–organic framework UiO-66 on the CO2 hydrogenation to formic acid were studied by force field-based molecular simulations. The confinement effects of UiO-66 and the metal–organic frameworks Cu-BTC, and IRMOF-1 were compared, to assess the impact of different pore size and metal centers on the production of HCOOH. Monte Carlo simulations in the grand-canonical ensemble were performed in the frameworks, using gas phase mole fractions of CO2, H2, and HCOOH at chemical equilibrium, obtained from Continuous Fractional Component Monte Carlo simulations in the Reaction Ensemble. The adsorption isobars of the components in metal–organic frameworks were computed at 298.15 – 800 K, 1 – 60 bar. The enhancement of HCOOH production due to preferential adsorption of HCOOH in metal–organic frameworks was calculated for all studied conditions. UiO-66, Cu-BTC, and IRMOF-1 affect CO2 hydrogenation reaction, shifting the thermodynamical equilibrium toward HCOOH formation. The prevailing factor is the type of metal center in the metal–organic framework. The confinement effect of Cu-BTC turns out to exceed the enhancement caused by UiO-66, and IRMOF-1. The resulting mole fraction of HCOOH increased by ca. 2000 times compared to the gas phase at 298.15 K, 60 bar. Cu-BTC can be considered as an alternative to improve the production of HCOOH due to elimination of the high-cost temperature elevation, cost reduction of downstream processing methods, and comparable final concentration of HCOOH to the reported concentrations of formate obtained using transition metal catalysts., Process and Energy

In this work, the added value of machine learning (ML) molecular force fields (FF) for the community of molecular simulations is showcased by successfully calculating transport properties of aqueous potassium hydroxide (KOH (aq)). Classical FFs use relatively simple interatomic potentials to simulate the nano scale. These simulations can predict macroscopic properties, such as density, heat of evaporation, viscosity, and self-diffusivity of the modeled materials. However, these FFs struggle to model materials in which more complicated interactions are relevant for the macroscopic behavior. Examples of such interactions are three-body interactions and chemical reactions. Quantum scale simulation methods are able to compute properties of materials in which these challenging interactions occur, although these methods are limited in length and time scales that can be modeled with realistic computational costs. Transport properties, such as viscosity, self-diffusivity and electric conductivity need these larger length and time scales to be determined accurately. ML can be used for a multi scale approach, bridging the gap between the quantum and the nano scale by training coefficients of general interatomic potentials. This provides the possibility of reaching the time and length scales of traditional molecular simulations with the accuracy of quantum mechanic models. KOH (aq) is selected to highlight the prospects of these multi scale techniques, as the self-diffusion of OH- in this electrolyte is dominated by proton transfer reactions, which has not been modeled successfully with classical FFs. Results of structure properties produced with ab initio molecular dynamics (AIMD, at quantum scale) simulations are compared with machine learning molecular dynamics (MLMD, at multi scale) simulations. There are no significant differences in the calculated shortest typical atomic distances and coordination numbers for both KOH (aq) and pure water systems. The determined, https://github.com/JelleLagerweij/Quantum_to_Transport GitHub repository with post-processing code and input files., Mechanical Engineering | Energy, Flow and Process Technology

Formic acid production from CO2 allows the reduction of carbon dioxide emissions while synthesizing a product with a wide range of applications. CO2 hydrogenation is challenging due to the cost of transition metal catalysts and the toxicity of the transition elements. In this work, the thermodynamic confinement effects of the metal–organic framework UiO-66 on the CO2 hydrogenation to formic acid were studied by force field-based molecular simulations. The confinement effects of UiO-66 and the metal–organic frameworks Cu-BTC, and IRMOF-1 were compared, to assess the impact of different pore size and metal centers on the production of HCOOH. Monte Carlo simulations in the grand-canonical ensemble were performed in the frameworks, using gas phase mole fractions of CO2, H2, and HCOOH at chemical equilibrium, obtained from Continuous Fractional Component Monte Carlo simulations in the Reaction Ensemble. The adsorption isobars of the components in metal–organic frameworks were computed at 298.15 – 800 K, 1 – 60 bar. The enhancement of HCOOH production due to preferential adsorption of HCOOH in metal–organic frameworks was calculated for all studied conditions. UiO-66, Cu-BTC, and IRMOF-1 affect CO2 hydrogenation reaction, shifting the thermodynamical equilibrium toward HCOOH formation. The prevailing factor is the type of metal center in the metal–organic framework. The confinement effect of Cu-BTC turns out to exceed the enhancement caused by UiO-66, and IRMOF-1. The resulting mole fraction of HCOOH increased by ca. 2000 times compared to the gas phase at 298.15 K, 60 bar. Cu-BTC can be considered as an alternative to improve the production of HCOOH due to elimination of the high-cost temperature elevation, cost reduction of downstream processing methods, and comparable final concentration of HCOOH to the reported concentrations of formate obtained using transition metal catalysts.

The foundation of all life is the interaction of molecules. Molecular interaction occurs in the tightly packed cytoplasm. In this crowded environment, the molecules need to be able to establish stable interactions with specific interaction partners, and with specific ones only. Selectivity is essential for transcriptional regulation where DNA-binding proteins, more specifically transcription factors, need to reach their respective target DNA, such as an operator sequence, quickly. The transcription factor LacI for example reaches its DNA operator within minutes and establishes a tight interaction to it that will block transcriptions of the genes it regulates. With the other millions of sequences in the bacterial chromosome, it interacts only fleetingly. This is possible because a small part of the protein is disordered during the transient interaction with non-operator DNA. Only with specific DNA will the folding of the disordered region into a rigid helix be favored. When the disordered region folds into a helix, the transcription factor changes its structure and, with it, its function from a weak DNA binder to a strong one. Thinking about molecular structures as dynamic entities that react to their environment and understanding the origins of structural metamorphosis allow us to predict changes in the protein sequence that will affect their behavior in the cellular context. This is demonstrated in this thesis where I study the structural dynamics of LacI with molecular dynamic simulations and use the insights from these simulations to design protein variants with changed binding stability and selectivity.

The foundation of all life is the interaction of molecules. Molecular interaction occurs in the tightly packed cytoplasm. In this crowded environment, the molecules need to be able to establish stable interactions with specific interaction partners, and with specific ones only. Selectivity is essential for transcriptional regulation where DNA-binding proteins, more specifically transcription factors, need to reach their respective target DNA, such as an operator sequence, quickly. The transcription factor LacI for example reaches its DNA operator within minutes and establishes a tight interaction to it that will block transcriptions of the genes it regulates. With the other millions of sequences in the bacterial chromosome, it interacts only fleetingly. This is possible because a small part of the protein is disordered during the transient interaction with non-operator DNA. Only with specific DNA will the folding of the disordered region into a rigid helix be favored. When the disordered region folds into a helix, the transcription factor changes its structure and, with it, its function from a weak DNA binder to a strong one. Thinking about molecular structures as dynamic entities that react to their environment and understanding the origins of structural metamorphosis allow us to predict changes in the protein sequence that will affect their behavior in the cellular context. This is demonstrated in this thesis where I study the structural dynamics of LacI with molecular dynamic simulations and use the insights from these simulations to design protein variants with changed binding stability and selectivity.

Speckle-type POZ protein (SPOP) is a substrate adaptor in the ubiquitin proteasome system, and plays important roles in cell-cycle control, development, and cancer pathogenesis. SPOP forms linear higher-order oligomers following an isodesmic self-association model. Oligomerization is essential for SPOP’s multivalent interactions with substrates, which facilitate phase separation and localization to biomolecular condensates. Structural characterization of SPOP in its oligomeric state and in solution is, however, challenging due to the inherent conformational and compositional heterogeneity of the oligomeric species. Here, we develop an approach to simultaneously and self-consistently characterize the conformational ensemble and the distribution of oligomeric states of SPOP by combining small-angle X-ray scattering (SAXS) and molecular dynamics (MD) simulations. We build initial conformational ensembles of SPOP oligomers using coarse-grained molecular dynamics simulations, and use a Bayesian/maximum entropy approach to refine the ensembles, along with the distribution of oligomeric states, against a concentration series of SAXS experiments. Our results suggest that SPOP oligomers behave as rigid, helical structures in solution, and that a flexible linker region allows SPOP’s substrate-binding domains to extend away from the core of the oligomers. Additionally, our results are in good agreement with previous characterization of the isodesmic self-association of SPOP. In the future, the approach presented here can be extended to other systems to simultaneously characterize structural heterogeneity and self-assembly., Speckle-type POZ protein (SPOP) is a substrate adaptor in the ubiquitin proteasome system, and plays important roles in cell-cycle control, development, and cancer pathogenesis. SPOP forms linear higher-order oligomers following an isodesmic self-association model. Oligomerization is essential for SPOP's multivalent interactions with substrates, which facilitate phase separation and localization to biomolecular condensates. Structural characterization of SPOP in its oligomeric state and in solution is, however, challenging due to the inherent conformational and compositional heterogeneity of the oligomeric species. Here, we develop an approach to simultaneously and self-consistently characterize the conformational ensemble and the distribution of oligomeric states of SPOP by combining small-angle X-ray scattering (SAXS) and molecular dynamics (MD) simulations. We build initial conformational ensembles of SPOP oligomers using coarse-grained molecular dynamics simulations, and use a Bayesian/maximum entropy approach to refine the ensembles, along with the distribution of oligomeric states, against a concentration series of SAXS experiments. Our results suggest that SPOP oligomers behave as rigid, helical structures in solution, and that a flexible linker region allows SPOP's substrate-binding domains to extend away from the core of the oligomers. Additionally, our results are in good agreement with previous characterization of the isodesmic self-association of SPOP. In the future, the approach presented here can be extended to other systems to simultaneously characterize structural heterogeneity and self-assembly.

Speckle-type POZ protein (SPOP) is a substrate adaptor in the ubiquitin proteasome system, and plays important roles in cell-cycle control, development, and cancer pathogenesis. SPOP forms linear higher-order oligomers following an isodesmic self-association model. Oligomerization is essential for SPOP’s multivalent interactions with substrates, which facilitate phase separation and localization to biomolecular condensates. Structural characterization of SPOP in its oligomeric state and in solution is, however, challenging due to the inherent conformational and compositional heterogeneity of the oligomeric species. Here, we develop an approach to simultaneously and self-consistently characterize the conformational ensemble and the distribution of oligomeric states of SPOP by combining small-angle X-ray scattering (SAXS) and molecular dynamics (MD) simulations. We build initial conformational ensembles of SPOP oligomers using coarse-grained molecular dynamics simulations, and use a Bayesian/maximum entropy approach to refine the ensembles, along with the distribution of oligomeric states, against a concentration series of SAXS experiments. Our results suggest that SPOP oligomers behave as rigid, helical structures in solution, and that a flexible linker region allows SPOP’s substrate-binding domains to extend away from the core of the oligomers. Additionally, our results are in good agreement with previous characterization of the isodesmic self-association of SPOP. In the future, the approach presented here can be extended to other systems to simultaneously characterize structural heterogeneity and self-assembly., Speckle-type POZ protein (SPOP) is a substrate adaptor in the ubiquitin proteasome system, and plays important roles in cell-cycle control, development, and cancer pathogenesis. SPOP forms linear higher-order oligomers following an isodesmic self-association model. Oligomerization is essential for SPOP's multivalent interactions with substrates, which facilitate phase separation and localization to biomolecular condensates. Structural characterization of SPOP in its oligomeric state and in solution is, however, challenging due to the inherent conformational and compositional heterogeneity of the oligomeric species. Here, we develop an approach to simultaneously and self-consistently characterize the conformational ensemble and the distribution of oligomeric states of SPOP by combining small-angle X-ray scattering (SAXS) and molecular dynamics (MD) simulations. We build initial conformational ensembles of SPOP oligomers using coarse-grained molecular dynamics simulations, and use a Bayesian/maximum entropy approach to refine the ensembles, along with the distribution of oligomeric states, against a concentration series of SAXS experiments. Our results suggest that SPOP oligomers behave as rigid, helical structures in solution, and that a flexible linker region allows SPOP's substrate-binding domains to extend away from the core of the oligomers. Additionally, our results are in good agreement with previous characterization of the isodesmic self-association of SPOP. In the future, the approach presented here can be extended to other systems to simultaneously characterize structural heterogeneity and self-assembly.

In F₀F₁-ATP synthase, proton translocation through F₀ drives rotation of the c-subunit oligomeric ring relative to the a-subunit. Recent studies suggest that in each step of the rotation, key glutamic acid residues in different c-subunits contribute to proton release to and proton uptake from the a-subunit. However, no studies have demonstrated cooperativity among c-subunits toward F₀F₁-ATP synthase activity. Here, we addressed this using Bacillus PS3 ATP synthase harboring a c-ring with various combinations of wild-type and cE56D, enabled by genetically fused single-chain c-ring. ATP synthesis and proton pump activities were decreased by a single cE56D mutation and further decreased by double cE56D mutations. Moreover, activity further decreased as the two mutation sites were separated, indicating cooperation among c-subunits. Similar results were obtained for proton transfer-coupled molecular simulations. The simulations revealed that prolonged proton uptake in mutated c-subunits is shared between two c-subunits, explaining the cooperation observed in biochemical assays.

We combine experiments and simulations to study the adsorption of water in several UiO-66 frameworks (ideal and defect-containing structures). We propose a new set of charges for the frameworks that accurately provides the water-structure interaction at the molecular level. The new set is suitable for predicting water adsorption in the ideal UiO-66 structure, providing for the first time, good agreement between experimental and calculated isotherms. The proposed procedure for tuning the point charges of the framework to achieve agreement with experiments is universal and can easily be extended to other MOFs. We explore the structural characteristics in terms of adsorption of water and the potential application of these materials to water harvesting from air. Our results show that the number of introduced defects significantly affect water sorption properties, which results in shifting steep water uptake and increasing saturation loading. Additional performed experiments, such as Ar sorption and the use of the QE-TPDA method allow for a broad characterization of structure-containing defects and the impact that these defects exert on the properties of the materials.

Aerobic life is powered by membrane-bound enzymes that catalyze the transfer of electrons to oxygen and protons across a biological membrane. Cytochrome c oxidase (CcO) functions as a terminal electron acceptor in mitochondrial and bacterial respiratory chains, driving cellular respiration and transducing the free energy from O2 reduction into proton pumping. Here we show that CcO creates orientated electric fields around a nonpolar cavity next to the active site, establishing a molecular switch that directs the protons along distinct pathways. By combining large-scale quantum chemical density functional theory (DFT) calculations with hybrid quantum mechanics/ molecular mechanics (QM/MM) simulations and atomistic molecular dynamics (MD) explorations, we find that reduction of the electron donor, heme a, leads to dissociation of an arginine (Arg438)–heme a3 D-propionate ion-pair. This ion-pair dissociation creates a strong electric field of up to 1 V Å-1 along a water-mediated proton array leading to a transient proton loading site (PLS) near the active site. Protonation of the PLS triggers the reduction of the active site, which in turn aligns the electric field vectors along a second, “chemical,” proton pathway. We find a linear energy relationship of the proton transfer barrier with the electric field strength that explains the effectivity of the gating process. Our mechanism shows distinct similarities to principles also found in other energy-converting enzymes, suggesting that orientated electric fields generally control enzyme catalysis.

Nanofiltration (NF) membranes are playing increasingly crucial roles in addressing emerging environmental challenges by precise separation, yet understanding of the selective transport mechanism is still limited. In this work, the underlying mechanisms governing precise selectivity of the polyamide NF membrane were elucidated using a series of monovalent cations with minor hydrated radius difference. The observed selectivity of a single cation was neither correlated with the hydrated radius nor hydration energy, which could not be explained by the widely accepted NF model or ion dehydration theory. Herein, we employed an Arrhenius approach combined with Monte Carlo simulation to unravel that the transmembrane process of the cation would be dominated by its pairing anion, if the anion has a greater transmembrane energy barrier, due to the constraint of anion–cation coupling transport. Molecular dynamics simulations further revealed that the distinct hydration structure was the primary origin of the energy barrier difference of cations. The cation having a larger incompressible structure after partial dehydration through subnanopores would induce a more significant ion–membrane interaction and consequently a higher energy barrier. Moreover, to validate our proposed mechanisms, a membrane grafting modification toward enlarging the energy barrier difference of dominant ions achieved a 3-fold enhancement in ion separation efficiency. Our work provides insights into the precise separation of ionic species by NF membranes.

The mitochondrial electron transport chain maintains the proton motive force that powers adenosine triphosphate (ATP) synthesis. The energy for this process comes from oxidation of reduced nicotinamide adenine dinucleotide (NADH) and succinate, with the electrons from this oxidation passed via intermediate carriers to oxygen. Complex IV (CIV), the terminal oxidase, transfers electrons from the intermediate electron carrier cytochrome c to oxygen, contributing to the proton motive force in the process. Within CIV, protons move through the K and D pathways during turnover. The former is responsible for transferring two protons to the enzyme’s catalytic site upon its reduction, where they eventually combine with oxygen and electrons to form water. CIV is the main site for respiratory regulation, and although previous studies showed that steroid binding can regulate CIV activity, little is known about how this regulation occurs. Here, we characterize the interaction between CIV and steroids using a combination of kinetic experiments, structure determination, and molecular simulations. We show that molecules with a sterol moiety, such as glyco-diosgenin and cholesteryl hemisuccinate, reversibly inhibit CIV. Flash photolysis experiments probing the rapid equilibration of electrons within CIV demonstrate that binding of these molecules inhibits proton uptake through the K pathway. Single particle cryogenic electron microscopy (cryo-EM) of CIV with glyco-diosgenin reveals a previously undescribed steroid binding site adjacent to the K pathway, and molecular simulations suggest that the steroid binding modulates the conformational dynamics of key residues and proton transfer kinetics within this pathway. The binding pose of the sterol group sheds light on possible structural gating mechanisms in the CIV catalytic cycle.

In the cellulose scientific community, hydrogen bonding is often used as the explanation for a large variety of phenomena and properties related to cellulose and cellulose based materials. Yet, hydrogen bonding is just one of several molecular interactions and furthermore is both relatively weak and sensitive to the environment. In this review we present a comprehensive examination of the scientific literature in the area, with focus on theory and molecular simulation, and conclude that the relative importance of hydrogen bonding has been, and still is, frequently exaggerated., QC 20220608

Free fatty acid receptor 1 (FFAR1) is a potential therapeutic target for the treatment of type 2 diabetes (T2D). It has been validated that agonists targeting FFAR1 can achieve the initial therapeutic endpoints of T2D, and the epimer agonists (R,S) AM-8596 can activate FFAR1 differently, with one acting as a partial agonist and the other as a full agonist. Up to now, the origin of the stereoselectivity of FFAR1 agonists remains elusive. In this work, we used molecular simulation methods to elucidate the mechanism of the stereoselectivity of the FFAR1 agonists (R)-AM-8596 and (S)-AM-8596. We found that the full agonist (R)-AM-8596 disrupts the residue interaction network around the receptor binding pocket and promotes the opening of the binding site for the G-protein, thereby resulting in the full activation of FFAR1. In contrast, the partial agonist (S)-AM-8596 forms stable electrostatic interactions with FFAR1, which stabilizes the residue network and hinders the conformational transition of the receptor. Our work thus clarifies the selectivity and underlying molecular activation mechanism of FFAR1 agonists., QC 20230510

Hydroquinone clathrates have been proposed as potential gas separation and storage media. Experimental results have demonstrated enhanced preferential adsorption for certain guest molecules, and also stability over temperature and pressure ranges that make them promising candidates to be employed in applications as hydrogen storage. Despite this, the characterization of these inclusion solids from thermodynamic and kinetic perspectives is still poor. In this work, we have tried to estimate the hydrogen storage ability of these clathrates using molecular simulations. The process of diffusion of hydrogen guest molecules from an external reservoir has been simulated using molecular dynamics, and the thermodynamic occupancy limit at different (T,p) conditions has been computed using hydrid Grand-Canonical Monte Carlo/Molecular Dynamics. The results show that hydrogen diffusion from an external reservoir is limited by interfacial phenomena in the clathrate surface, and also that multiple guest occupancy and its distribution can be computed using the described approach

Modern thermodynamic models incorporate the concept of association (hydrogen bonding) and they can describe very satisfactorily many properties of water containing mixtures. They have not been successful in representing water's anomalous properties and this work provides a possible explanation. We have analyzed and interpreted recent experimental data, molecular simulation results, and two-state theory approaches and compared against the predictions from several thermodynamic models. We show that the dominance of the tetrahedral structure implemented in modern thermodynamic models may be the reason for their failure for describing water systems. While this study does not prove the two-state theories for water, it indicates that a high level of tetrahedral structure of water is not in agreement with water's anomalous properties when used in thermodynamic models.

We combine experiments and simulations to study the adsorption of water in several UiO-66 frameworks (ideal and defect-containing structures). We propose a new set of charges for the frameworks that accurately provides the water-structure interaction at the molecular level. The new set is suitable for predicting water adsorption in the ideal UiO-66 structure, providing for the first time, good agreement between experimental and calculated isotherms. The proposed procedure for tuning the point charges of the framework to achieve agreement with experiments is universal and can easily be extended to other MOFs. We explore the structural characteristics in terms of adsorption of water and the potential application of these materials to water harvesting from air. Our results show that the number of introduced defects significantly affect water sorption properties, which results in shifting steep water uptake and increasing saturation loading. Additional performed experiments, such as Ar sorption and the use of the QE-TPDA method allow for a broad characterization of structure-containing defects and the impact that these defects exert on the properties of the materials.

The conformational heterogeneity of a folded protein can affect not only its function but also stability and folding. We recently discovered and characterized a stabilized double mutant (L49I/I57V) of the protein CI2 and showed that state-of-the-art prediction methods could not predict the increased stability relative to the wild-type protein. Here, we have examined whether changed native-state dynamics, and resulting entropy changes, can explain the stability changes in the double mutant protein, as well as the two single mutant forms. We have combined NMR relaxation measurements of the ps-ns dynamics of amide groups in the backbone and the methyl groups in the side chains with molecular dynamics simulations to quantify the native-state dynamics. The NMR experiments reveal that the mutations have different effects on the conformational flexibility of CI2: a reduction in conformational dynamics (and entropy estimated from this) of the native state of the L49I variant correlates with its decreased stability, while increased dynamics of the I57V and L49I/I57V variants correlates with their increased stability. These findings suggest that explicitly accounting for changes in native-state entropy might be needed to improve the predictions of the effect of mutations on protein stability.

The conformational heterogeneity of a folded protein can affect not only its function but also stability and folding. We recently discovered and characterized a stabilized double mutant (L49I/I57V) of the protein CI2 and showed that state-of-the-art prediction methods could not predict the increased stability relative to the wild-type protein. Here, we have examined whether changed native-state dynamics, and resulting entropy changes, can explain the stability changes in the double mutant protein, as well as the two single mutant forms. We have combined NMR relaxation measurements of the ps-ns dynamics of amide groups in the backbone and the methyl groups in the side chains with molecular dynamics simulations to quantify the native-state dynamics. The NMR experiments reveal that the mutations have different effects on the conformational flexibility of CI2: a reduction in conformational dynamics (and entropy estimated from this) of the native state of the L49I variant correlates with its decreased stability, while increased dynamics of the I57V and L49I/I57V variants correlates with their increased stability. These findings suggest that explicitly accounting for changes in native-state entropy might be needed to improve the predictions of the effect of mutations on protein stability.

Most of the sedimentary carbonates deposited in the marine environments are composed of calcium carbonate minerals with varying amounts of incorporated Mg2+. However, understanding how interactions of impurities with carbonate and their incorporation affect sediments behavior remains a challenge. Here, a new insight is obtained by monitoring solution composition, morphology, and electrokinetic potential of carbonate particles formed in a spontaneous unseeded batch precipitation experiment using electrochemical and scanning electron microscopy methods. The solid composition and growth rate are extracted from changes in the bulk composition and fitted to chemical affinity rate law, revealing that the precipitation pathway consists of second-order dissolution and first-order precipitation. The molecular dynamics simulations show that the lattice strain induced by randomly substituting Ca2+ by Mg2+ stabilizes spherical nanoparticles and reduces their surface area and volume. Combining kinetics and thermodynamics insight, we conclude that variation in the carbonate bulk and interfacial energies, along with the solution supersaturation, lead to the dissolution-precipitation transformation pathway from Mg-rich to Mg-poor carbonate phase that preserves spherulitic morphology. Our findings are relevant for long-standing questions of how impurities influence diagenesis of carbonate sediments and spherulitic carbonate particles' origin.

Using a combination of molecular simulations techniques, we evaluate the structural tunability of the metal azolate framework with zeolitic RHO topology, MAF-6. Two mechanisms are explored to induce hydrophilicity to this hydrophobic material. The study at a molecular level of water adsorption takes place under a variety of conditions. On a first step, we consider water mixtures containing benzene or alcohols, paying special attention to the effect of the size of the alcohol molecules. On a second approach, we analyse the effect of small weight percentages of salt into the MAF-6 on the water adsorption. We first validate the accuracy of the host–guest interactions by reproducing experimental data. A new set of Lennard-Jones parameters for the interaction water- MAF-6 is also provided. The water adsorption behaviour of MAF-6 is studied in terms of adsorption isotherms, heats of adsorption, radial distribution functions, hydrogen bonds formation, and water distribution inside the material. We found that the presence of long molecules of alcohols favours the water adsorption at low values of pressure by smoothing the phase transition of water withing the MAF-6. On the other hand the addition of salt to the structure creates additional adsorption sites for water enhancing its adsorption, while reducing the saturation capacity of the material since the presence of salt reduces the accessible pore volume.

Figure S1: Convergence of the total energy with plane wave cut-off and k point sampling mesh for MAF-66. Figure S2: Pore size distributions of MAF-66 (left) and ZTF (right). Figure S3: DFT optimized structures of parts of the supercells of ZTF (left) and MAF-66 (right) with one CO2 molecule inside. Figure S4: DFT optimized structure of parts of the supercell of MOF-66 with of one water molecule inside.

In search for future good adsorbents for CO2 capture, a nitrogen-rich triazole-type Metal-Organic Framework (MOF) is proposed based on the rational design and theoretical molecular simulations. The structure of the proposed MOF, named Zinc Triazolate based Framework (ZTF), is obtained by replacing the amine-organic linker of MAF-66 by a triazole, and its structural parameters are deduced. We used grand-canonical Monte Carlo (GCMC) simulations based on generic classical force fields to correctly predict the adsorption isotherms of CO2 and H2O. For water adsorption in MAF-66 and ZTF, simulations revealed that the strong hydrogen bonding interactions of water with the N atoms of triazole rings of the frameworks are the main driving forces for the high adsorption uptake of water. We also show that the proposed ZTF porous material exhibits exceptional high CO2 uptake capacity at low pressure, better than MAF-66. Moreover, the nature of the interactions between CO2 and the MAF-66 and ZTF surface cavities was examined at the microscopic level. Computations show that the interactions occur at two different sites, consisting of Lewis acid-Lewis base interactions and hydrogen bonding, together with obvious electrostatic interactions. In addition, we investigated the influence of the presence of H2O molecules on the CO2 adsorption on the ZTF MOF. GCMC simulations reveal that the addition of H2O molecules leads to an enhancement of the CO2 adsorption at very low pressures but a reduction of this CO2 adsorption at higher pressures.

Understanding of drug–carrier interactions is essential for the design and application of metal–organic framework (MOF)-based drug-delivery systems, and such drug–carrier interactions can be fundamentally different for MOFs with or without defects. Herein, we reveal that the defects in MOFs play a key role in the loading of many pharmaceuticals with phosphate or phosphonate groups. The host–guest interaction is dominated by the Coulombic attraction between phosphate/phosphonate groups and defect sites, and it strongly enhances the loading capacity. For similar molecules without a phosphate/phosphonate group or for MOFs without defects, the loading capacity is greatly reduced. We employed solid-state NMR spectroscopy and molecular simulations to elucidate the drug–carrier interaction mechanisms. Through a synergistic combination of experimental and theoretical analyses, the docking conformations of pharmaceuticals at the defects were revealed., QC 20211215

Cellular respiration is powered by membrane-bound redox enzymes that convert chemical energy into an electrochemical proton gradient and drive the energy metabolism. By combining large-scale classical and quantum mechanical simulations with cryo-electron microscopy data, we resolve here molecular details of conformational changes linked to proton pumping in the mammalian complex I. Our data suggest that complex I deactivation blocks water-mediated proton transfer between a membrane bound quinone site and proton-pumping modules, decoupling the energy-transduction machinery. We identify a putative gating region at the interface between membrane domain subunits ND1 and ND3/ND4L/ND6 that modulates the proton transfer by conformational changes in transmembrane helices and bulky residues. The region is perturbed by mutations linked to human mitochondrial disorders and is suggested to also undergo conformational changes during catalysis of simpler complex I variants that lack the "active"-to-"deactive" transition. Our findings suggest that conformational changes in transmembrane helices modulate the proton transfer dynamics by wetting/dewetting transitions and provide important functional insight into the mammalian respiratory complex I.

Most of the sedimentary carbonates deposited in the marine environments are composed of calcium carbonate minerals with varying amounts of incorporated Mg2+. However, understanding how interactions of impurities with carbonate and their incorporation affect sediments behavior remains a challenge. Here, a new insight is obtained by monitoring solution composition, morphology, and electrokinetic potential of carbonate particles formed in a spontaneous unseeded batch precipitation experiment using electrochemical and scanning electron microscopy methods. The solid composition and growth rate are extracted from changes in the bulk composition and fitted to chemical affinity rate law, revealing that the precipitation pathway consists of second-order dissolution and first-order precipitation. The molecular dynamics simulations show that the lattice strain induced by randomly substituting Ca2+ by Mg2+ stabilizes spherical nanoparticles and reduces their surface area and volume. Combining kinetics and thermodynamics insight, we conclude that variation in the carbonate bulk and interfacial energies, along with the solution supersaturation, lead to the dissolution-precipitation transformation pathway from Mg-rich to Mg-poor carbonate phase that preserves spherulitic morphology. Our findings are relevant for long-standing questions of how impurities influence diagenesis of carbonate sediments and spherulitic carbonate particles' origin.

The reaction of the V-shaped linker molecule 5-hydroxyisophthalic acid (H2L0), with Al or Ga nitrate under almost identical reaction conditions leads to the nitration of the linker and subsequent formation of metal-organic frameworks (MOFs) with CAU-10 or MIL-53 type structure of composition [Al(OH)(L)], denoted as Al-CAU-10-L-0,L- 2,L- 4,L- 6 or [Ga(OH)(L)], denoted as Ga-MIL-53-L-2. The Al-MOF contains the original linker L-0 as well as three different nitration products (L-2, L-4 and L-4/6), whereas the Ga-MOF mainly incorporates the linker L-2. The compositions were deduced by H-1 NMR spectroscopy and confirmed by Rietveld refinement. In situ and ex situ studies were carried out to follow the nitration and crystallization, as well as the composition of the MOFs. The crystal structures were refined against powder X-ray diffraction (PXRD) data. As anticipated, the use of the V-shaped linker results in the formation of the CAU-10 type structure in the Al-MOF. Unexpectedly, the Ga-MOF crystallizes in a MIL-53 type structure, which is usually observed with linear or slightly bent linker molecules. To study the structure directing effect of the in situ nitrated linker, pure 2-nitrobenzene-1,3-dicarboxylic acid (m-H2BDC-NO2) was employed which exclusively led to the formation of [Ga(OH)(C8H3NO6)] (Ga-MIL-53-m-BDC-NO2), which is isoreticular to Ga-MIL-53-L-2. Density Functional Theory (DFT) calculations confirmed the higher stability of Ga-MIL-53-L-2 compared to Ga-CAU-10-L-2 and grand canonical Monte Carlo simulations (GCMC) are in agreement with the observed water adsorption isotherms of Ga-MIL-53-L-2.

The interest in mechanochemical research has dramatically increased in recent years with the advent of computational chemistry tools where detailed reaction thermodynamics, and kinetics can be studied. However, most chemistry software packages do not address mechanochemical phenomena and computational chemists need to modify a quantum chemical software to perform specialized simulations. Current implementation includes Force Modified Potential Energy Surface (FMPES), External Force Explicitly Included (EFEI), and Enforce Geometry Optimizations (EGO) formalisms. This also includes a wall potential based function to simulate mechanical grinding. In this work, a Python module that allows inclusion of external forces during molecular geometry optimizations and molecular dynamics simulations while virtually employing any quantum chemical or molecular mechanical software is presented. It is expected that OpenMechanochem will facilitate mechanochemical reaction simulations that will explain the interplay of external forces to a chemical system. (C) 2021 The Authors. Published by Elsevier B.V.

Intrinsically disordered proteins (IDPs) are widely distributed across eukaryotic cells, playing important roles in molecular recognition, molecular assembly, post-translational modification, and other biological processes. IDPs are also associated with many diseases such as cancers, cardiovascular diseases, and neurodegenerative diseases. Due to their structural flexibility, conventional experimental methods cannot reliably capture their heterogeneous structures. Molecular dynamics simulation becomes an important complementary tool to quantify IDP structures. This review covers recent force field strategies proposed for more accurate molecular dynamics simulations of IDPs. The strategies include adjusting dihedral parameters, adding grid-based energy correction map (CMAP) parameters, refining protein-water interactions, and others. Different force fields were found to perform well on specific observables of specific IDPs but also are limited in reproducing all available experimental observables consistently for all tested IDPs. We conclude the review with perspective areas for improvements for future force fields for IDPs.

We present the results of a combined experimental-molecular simulations approach concerning the capacity for CO2 adsorption of aminosilica hybrid products synthesized using supercritical fluids. Two porous supports were examined for amine functionalization, an ordered mesoporous silica (MCM-41) and a disordered silica gel (SG40). The textural properties of the studied materials were analyzed by low-temperature N2 adsorption-desorption isotherms and compared to those of molecular simulations using the grand canonical Monte Carlo simulation method. The CO2 adsorption capacity of these materials was evaluated by recording CO2 adsorption isotherms up to 100 kPa. Molecular simulations of the CO2 adsorption behavior of selected samples were performed to gain a fundamental understanding of the effect of functionalization. This study shows that in the functionalized materials, the distance between nitrogen atoms of the grafted amines is a critical factor for the occurrence of CO2 chemisorption, providing some insight into key parameters for designing adsorbent materials for CO2 capture and separation. The relationship between the adsorption results with N2 and CO2 allow us to compare the potential applications of the materials in CO2 adsorption and separation processes. A correlation of the N2 adsorption at a given pressure with the CO2 adsorption at a different pressure allowed the prediction of which materials will perform well for these processes. The hybrid products with high amine density have desirable features required for industrial sorbents, such as an enhanced CO2 adsorption capacity and selectivity. © 2015 American Chemical Society.

The present work focuses on the development of a new eco-efficient chemical method for the polymerization of aziridine to hyperbranched polyethyleneimine (PEI) into mesoporous silica by using compressed CO2 as a solvent, reaction medium and catalyst. PEI was in situ grafted into MCM-41 and silica gel substrates, with pore diameters of 3.8 and 9.0 nm, respectively. The optimal polymerization conditions were found by varying the reaction pressure (1.0-10 MPa), temperature (25-45°C) and time (20-400 min). The thermal stability analysis indicated that aminopolymer chains were covalently attached on the amorphous silica surface. The described compressed CO2 route for the synthesis of high amine content hybrid products (6-8 mmolN g-1) is a very fast method, with processing times in the order of few minutes even at very low working pressures (1.0 MPa), being a step forward in the design of efficient hybrid aminopolymer nanocomposites for CO2 capture. The adsorptive behavior of the prepared hybrid materials was experimentally established by recording the N2 (-196°C) and CO2 (25, 50 and 75°C) adsorption isotherms. Results were compared to molecular simulation studies performed using Grand Canonical Monte Carlo for either N2 or CO2 adsorbed on amino modified MCM-41, thus helping to elucidate the predominant PEI configuration present in the functionalized materials. © The Royal Society of Chemistry 2015.

The interest in mechanochemical research has dramatically increased in recent years with the advent of computational chemistry tools where detailed reaction thermodynamics, and kinetics can be studied. However, most chemistry software packages do not address mechanochemical phenomena and computational chemists need to modify a quantum chemical software to perform specialized simulations. Current implementation includes Force Modified Potential Energy Surface (FMPES), External Force Explicitly Included (EFEI), and Enforce Geometry Optimizations (EGO) formalisms. This also includes a wall potential based function to simulate mechanical grinding. In this work, a Python module that allows inclusion of external forces during molecular geometry optimizations and molecular dynamics simulations while virtually employing any quantum chemical or molecular mechanical software is presented. It is expected that OpenMechanochem will facilitate mechanochemical reaction simulations that will explain the interplay of external forces to a chemical system. (C) 2021 The Authors. Published by Elsevier B.V.

In search for future good adsorbents for CO2 capture, a nitrogen-rich triazole-type Metal-Organic Framework (MOF) is proposed based on the rational design and theoretical molecular simulations. The structure of the proposed MOF, named Zinc Triazolate based Framework (ZTF), is obtained by replacing the amine-organic linker of MAF-66 by a triazole, and its structural parameters are deduced. We used grand-canonical Monte Carlo (GCMC) simulations based on generic classical force fields to correctly predict the adsorption isotherms of CO2 and H2O. For water adsorption in MAF-66 and ZTF, simulations revealed that the strong hydrogen bonding interactions of water with the N atoms of triazole rings of the frameworks are the main driving forces for the high adsorption uptake of water. We also show that the proposed ZTF porous material exhibits exceptional high CO2 uptake capacity at low pressure, better than MAF-66. Moreover, the nature of the interactions between CO2 and the MAF-66 and ZTF surface cavities was examined at the microscopic level. Computations show that the interactions occur at two different sites, consisting of Lewis acid-Lewis base interactions and hydrogen bonding, together with obvious electrostatic interactions. In addition, we investigated the influence of the presence of H2O molecules on the CO2 adsorption on the ZTF MOF. GCMC simulations reveal that the addition of H2O molecules leads to an enhancement of the CO2 adsorption at very low pressures but a reduction of this CO2 adsorption at higher pressures.

Figure S1: Convergence of the total energy with plane wave cut-off and k point sampling mesh for MAF-66. Figure S2: Pore size distributions of MAF-66 (left) and ZTF (right). Figure S3: DFT optimized structures of parts of the supercells of ZTF (left) and MAF-66 (right) with one CO2 molecule inside. Figure S4: DFT optimized structure of parts of the supercell of MOF-66 with of one water molecule inside.

Using a combination of molecular simulations techniques, we evaluate the structural tunability of the metal azolate framework with zeolitic RHO topology, MAF-6. Two mechanisms are explored to induce hydrophilicity to this hydrophobic material. The study at a molecular level of water adsorption takes place under a variety of conditions. On a first step, we consider water mixtures containing benzene or alcohols, paying special attention to the effect of the size of the alcohol molecules. On a second approach, we analyse the effect of small weight percentages of salt into the MAF-6 on the water adsorption. We first validate the accuracy of the host–guest interactions by reproducing experimental data. A new set of Lennard-Jones parameters for the interaction water- MAF-6 is also provided. The water adsorption behaviour of MAF-6 is studied in terms of adsorption isotherms, heats of adsorption, radial distribution functions, hydrogen bonds formation, and water distribution inside the material. We found that the presence of long molecules of alcohols favours the water adsorption at low values of pressure by smoothing the phase transition of water withing the MAF-6. On the other hand the addition of salt to the structure creates additional adsorption sites for water enhancing its adsorption, while reducing the saturation capacity of the material since the presence of salt reduces the accessible pore volume.

The relevant parts of the microstructure participating in the plastic deformation of glassy polystyrene are identified. This is achieved by performing quasi-static deformation simulations of an atomistic representation of polystyrene, within a thermodynamic framework, under experimentally realistic boundary conditions (controlled compressive strain, atmospheric pressure in the lateral directions, and room temperature). In particular, it is shown that discontinuities in the free energy in the course of deformation are representative of microscopic plastic events, which are strongly correlated with the heterogeneous non-affine deformation of the phenyl-rings. However, despite the induced anisotropy during deformation, the phenyl-rings do not show any preferred orientation during deformation. The rearrangements of the microstructure during the discontinuities are analyzed further in terms of a local best-fit deformation gradient tensor (a modified version of the procedure introduced by Falk and Langer in 1998) as well as the stretch- and rotation-components of the local deformation of clusters of atoms that show significant non-affine deformation. This analysis shows that the local deformation is highly heterogeneous, and locally the strains and rotations can be orders of magnitude larger than the imposed deformation, giving rise to plastic deformation of the material.

In recent years the use of integrative, information-driven computational approaches for modelling the structure of biomolecules has been increasing in popularity. These are now recognised as a crucial complement to experimental structural biology techniques such as X-ray crystallography, Nuclear Magnetic Resonance (NMR) spectroscopy and cryo-electron microscopy (cryo-EM). This trend can be credited to a few reasons such as the increased prominence of structures solved by cryo-EM, the improvements in proteomics approaches such as Crosslinking Mass Spectrometry (XL-MS), the drive to study systems of higher complexity in their native state and the maturation of many computational techniques combined with the wide-spread availability of information-driven integrative modelling platforms.In this review we highlight recent works that exemplify how the use of integrative and/or information-driven approaches and platforms can produce highly accurate structural models. These examples include systems which present many challenges when studied with traditional structural biology techniques such as flexible and dynamic macromolecular assemblies and membrane associated complexes.We also identify some key areas of interest for information-driven, integrative modelling and discuss how they relate to ongoing challenges in the fields of computational structural biology. These include the use of coarse-grained forcefields for biomolecular simulations – allowing for simulations across longer (time-) and bigger (size-dimension) scales –, the use of bioinformatics predictions to drive sampling and/or scoring in docking such as those derived from coevolution analysis, and finally the study of membrane and membrane-associated protein complexes.