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We demonstrate and characterize a first-principles approach to modeling the mass action dynamics of metabolism. Starting from a basic definition of entropy expressed as a multinomial probability density using Boltzmann probabilities with standard chemical potentials, we derive and compare the free energy dissipation and the entropy production rates. We express the relation between entropy production and the chemical master equation for modeling metabolism, which unifies chemical kinetics and chemical thermodynamics. Because prediction uncertainty with respect to parameter variability is frequently a concern with mass action models utilizing rate constants, we compare and contrast the maximum entropy model, which has its own set of rate parameters, to a population of standard mass action models in which the rate constants are randomly chosen. We show that a maximum entropy model is characterized by a high probability of free energy dissipation rate and likewise entropy production rate, relative to other models. We then characterize the variability of the maximum entropy model predictions with respect to uncertainties in parameters (standard free energies of formation) and with respect to ionic strengths typically found in a cell. [ABSTRACT FROM AUTHOR]

Determining fluid pressure in Monte Carlo simulations can be a challenging task due to the reduced arsenal of computational tools available to perform such measurements. In addition, none of these tools is general enough to calculate the equilibrium pressure for a wide variety of models. The Gibbs–Duhem method, for example, is a very useful option, but only for pure (one component) systems. To enrich this arsenal, we propose here a direct method to calculate pressure in the canonical ensemble, which could easily be extended to mixtures at low densities. In analogy with the Widom method, our approach is based on the free energy variation with volume, described in terms of the removal of an empty or particle-occupied lattice column. We tested our approach for the lattice gas model and compared the results with exact Onsager solutions. Furthermore, the appearance of thermodynamic instabilities (loops) in the pressure isotherms during the phase transition and their relationship with interface effects are discussed. Finally, a phase diagram is obtained from these isotherms using the Hill construction. [ABSTRACT FROM AUTHOR]

We show that the height function of the six-vertex model, in the parameter range a D b D 1 and c > 1, is delocalized with logarithmic variance when c > 2. This complements the earlier proven localization for c > 2. Our proof relies on Russo-Seymour-Welsh type arguments, and on the local behaviour of the free energy of the cylindrical six-vertex model, as a function of the unbalance between the number of up and down arrows. [ABSTRACT FROM AUTHOR]

Thermodynamics is a fundamental topic of continuum mechanics and biomechanics, with a wide range of applications to physiological and biological processes. This study addresses two fundamental limitations of current thermodynamic treatments. First, thermodynamics tables distributed online by the U.S. National Institute of Standards and Technology (NIST) report properties of fluids as a function of absolute temperature T and absolute pressure P. These properties include mass density p, specific internal energy u, enthalpy h = u + P/p, and entropy s. However, formulations of jump conditions across phase boundaries derived from Newton's second law of motion and the first law of thermodynamics employ the gauge pressure p = P - Pr, where P, is an arbitrarily selected referential absolute pressure. Interchanging p with P is not innocuous as it alters tabulated NIST values for u while keeping h and s unchanged. Using p for functions of state and governing equations solves the problem with using NIST entries for the specific internal energy u in standard thermodynamics tables and analyses of phase transformation in continuum mechanics. Second, constitutive models for the free energy of fluids, such as water and air, are not typically provided in standard thermodynamics treatments. This study proposes a set of constitutive models and validates them against suitably modified NIST data. [ABSTRACT FROM AUTHOR]

The investigation of condensed matter transformations hinges on the precision of free-energy calculations. This article charts the evolution of molecular simulations, tracing their development from the techniques of the early 1960s, through the emergence of free-energy calculations toward the end of the decade, and leading to the advent of umbrella sampling in 1977. The discussion explores the inherent challenges and limitations of early simulational endeavors, such as the struggle with accurate phase-space sampling and the need for innovative solutions like importance sampling and multistage sampling methods. Taken together, the initial hurdles and subsequent adoption of advanced techniques exemplify the leap from analytical methods to effective computational strategies that enabled more reliable simulations. Further analysis of this narrative reveals the methodological breakthroughs as well as the setbacks that transformed the theoretical and practical understanding of condensed matter phenomena. A follow-up study will examine the shifts in free-energy calculations from the late 1970s into the 1980s. [ABSTRACT FROM AUTHOR]

A dense artificial neural network, ESE-ΔH-DNN, with two hidden layers for calculating both solvation free energies ΔG°solv and enthalpies ΔH°solv for neutral solutes in organic solvents is proposed. The input features are generalized-Born-type monatomic and pair electrostatic terms, the molecular volume, and atomic surface areas of the solute, as well as five easily available properties of the solvent. ESE-ΔH-DNN is quite accurate for ΔG°solv, with an RMSE (root mean square error) below 0.6 kcal/mol and an MAE (mean absolute error) well below 0.4 kcal/mol. It performs particularly well for alkane, aromatic, ester, and ketone solvents. ESE-ΔH-DNN also exhibits a fairly good accuracy for ΔH°solv prediction, with an RMSE below 1 kcal/mol and an MAE of about 0.6 kcal/mol. [ABSTRACT FROM AUTHOR]

Years of massive applications of high-throughput atomistic modeling tools such as molecular docking and end-point free energy calculations in the drug industry and academic exploration have made them indispensable parts of hierarchical screening. While the similarities between host–guest and protein–ligand complexes lead to the direct extension of techniques for protein–ligand screening to host–guest systems, the practical performance of these hit identification tools remains unclear in host-–-guest binding. Recent reports on specific host–guest complexes suggest that the experience on the accuracy ladder accumulated from protein–ligand cases could be invalid in host–guest complexes, which makes it an urgent need to perform a systematic benchmark to secure solid numerical supports and guidance of practical setups. Concerning molecular docking, there still lacks a comprehensive benchmark considering popular docking programs. As for end-point reranking, quantitative and rigorous free energy estimation via end-point formulism requires establishing statistically meaningful measurements of uncertainties due to finite sampling, which is neglected or underestimated by a significant portion in almost all main-stream applications. Further, a face-to-face comparison between different screening tools is required for the design of a hierarchical workflow. To fill the above-mentioned critical gaps, in this work, using a dataset containing tens of host–guest complexes involving basket-like macromolecular hosts from the octa acid family, we extensively benchmark seven academic docking protocols and perform post-docking end-point rescoring with twenty protocols. The resulting comprehensive benchmark provides conclusive pictures of the practical value of docking and end-point screening in OA host–guest binding. [ABSTRACT FROM AUTHOR]

Nucleation is a fundamental and general process at the initial stage of first-order phase transition. Although various models based on the classical nucleation theory (CNT) have been proposed to explain the energetics and kinetics of nucleation, detailed understanding at nanoscale is still required. Here, in view of the homogeneous bubble nucleation, we focus on cavity formation, in which evaluation of the size dependence of free energy change is the key issue. We propose the application of a formula in stochastic thermodynamics, the Jarzynski equality, for data analysis of molecular dynamics (MD) simulation to evaluate the free energy of cavity formation. As a test case, we performed a series of MD simulations with a Lennard-Jones (LJ) fluid system. By applying an external spherical force field to equilibrated LJ liquid, we evaluated the free energy change during cavity growth as the Jarzynski's ensemble average of required works. A fairly smooth free energy curve was obtained as a function of bubble radius in metastable liquid of mildly negative pressure conditions. [ABSTRACT FROM AUTHOR]

The recently developed efficient protocols to implicit [Grimme et al., J. Phys. Chem. A 125, 4039–4054 (2021)] and explicit quantum mechanical modeling of non-rigid molecules in solution [Katsyuba et al., J. Phys. Chem. B 124, 6664–6670 (2020)] are used to describe conformational equilibria of 1,2-dichloroethane and 1,2-dibromoethane in various media. Two approaches for evaluation of trans/gauche free energy differences, ΔGt-g, are compared: (a) direct ΔGt-g computation in implicit solution; (b) the use, together with experimental intensities, of infrared absorption coefficients and Raman scattering cross sections computed for each explicitly modeled solution. The same cluster model of a solute surrounded by the first solvation shell of solvent molecules was used to simulate both Raman and IR spectra. The good agreement between the two approaches indicates the reliability of both methods. The importance of using correct absorption coefficients and Raman scattering factors for each medium is discussed. The ΔGt-g estimates from both implicit and explicit solvation simulations were combined with experimentally measured enthalpy differences ΔHt-g available in the literature to obtain condensed-state ΔSt-g estimates. [ABSTRACT FROM AUTHOR]

The chemical potential of a component in a solution is defined as the free energy change as the amount of that component changes. Computing this fundamental thermodynamic property from atomistic simulations is notoriously difficult because of the convergence issues involved in free energy methods and finite size effects. This Communication presents the so-called S0 method, which can be used to obtain chemical potentials from static structure factors computed from equilibrium molecular dynamics simulations under the isothermal–isobaric ensemble. This new method is demonstrated on the systems of binary Lennard-Jones particles, urea–water mixtures, a NaCl aqueous solution, and a high-pressure carbon–hydrogen mixture. [ABSTRACT FROM AUTHOR]

We compute the energetic cost of formation of Janus particle structures. Using an approach that couples particle dynamics to the evolution of fuel concentration in the medium, which we consider to be initially inhomogeneous, we show the different types of emerging structures. The energy dissipated in the formation of such structures is obtained from the entropy production rate, which is a non-monotonic function of the fraction of assembled particles and, thus, different in each self-assembly regime. An analysis of the free energy of these particles allows us to establish a thermodynamic criterion of structure formation based on the behavior of chemical potential as a function of the fraction of assembled particles. [ABSTRACT FROM AUTHOR]

This paper studies moisture damage resistance from the perspective of adhesion. The old asphalt in reclaimed asphalt pavement (RAP) is recovered using the extraction method, centrifugal impurity removal and distillation recovery method. Effects of an asphalt rejuvenator on the physical and rheological properties of new and old asphalt are studied. The surface free energy (SFE) parameters of asphalt and aggregate are measured and calculated using the sessile drop and vapour adsorption methods, respectively. The cohesion and adhesive bond energy, and the moisture stability index ER value of asphalt and aggregate, are calculated based on the Good-van Oss-Chaudhury (GvOC) theoretical system. The results show that the addition of an asphalt rejuvenator has a significant recovery effect on the physical and rheological properties of old asphalt. When the content of the asphalt rejuvenator is 4%, it can be restored to the level of new asphalt. When the content of the asphalt rejuvenator is between 3% and 4%, it is similar to that of new asphalt. However, the asphalt rejuvenator has a negative effect on the high-temperature and adhesion properties of new asphalt. [ABSTRACT FROM AUTHOR]

The present study utilized the ab initio atomistic thermodynamics technique to assess the stability of pure carbon dioxide and pure methane on the calcite(10.4) systems. The stability of configurations 0.5 ML-A2, 0.75 ML-A2, and 0.75 ML-A1 in CH4/calcite (10.4) systems was shown to be considerable, but only within a limited range of chemical potential. The 1.0 ML-A1 and 1.0 ML-A2 systems of CH4/calcite (10.4) demonstrated remarkable stability throughout a wide range of chemical potentials. The predominant stable forms for CO2/calcite (10.4) systems are the 1.0 ML-B2 and 1.0 ML-A4 structures. The surface free energy phase diagrams demonstrate that CO2 is more favourable than CH4 for adsorption on the calcite (10.4) surface. Paper type: Short communication paper [ABSTRACT FROM AUTHOR]

Catalan's SPPN, a measure of solvent polarity/polarizability has been analysed in terms of molecular properties derived from computational chemistry. The results show that SPPN correlates positively with the molecular dipole moment and quadrupolar amplitude and negatively with the molecular polarizability. These correlations are shared with Kamet and Taft's π* and Reichardt and Dimroth's ET(30). Thus, one can associate the solvent polarity with non-specific interactions involving the permanent charges on solvent molecules. It is also noted that the opposite correlations, all three parameters increasing with increasing solvent polarity but decreasing with increasing solvent polarizability, creates an ambiguity in their use, for example, in linear free energy relationships. [ABSTRACT FROM AUTHOR]

Given a chemical reaction going from reactant (R) to the product (P) on a potential energy surface (PES) and a collective variable (CV) discriminating between R and P, we define the free-energy profile (FEP) as the logarithm of the marginal Boltzmann distribution of the CV. This FEP is not a true free energy. Nevertheless, it is common to treat the FEP as the "free-energy" analog of the minimum potential energy path and to take the activation free energy, Δ F RP ‡ , as the difference between the maximum at the transition state and the minimum at R. We show that this approximation can result in large errors. The FEP depends on the CV and is, therefore, not unique. For the same reaction, different discriminating CVs can yield different Δ F RP ‡ . We derive an exact expression for the activation free energy that avoids this ambiguity. We find Δ F RP ‡ to be a combination of the probability of the system being in the reactant state, the probability density on the dividing surface, and the thermal de Broglie wavelength associated with the transition. We apply our formalism to simple analytic models and realistic chemical systems and show that the FEP-based approximation applies only at low temperatures for CVs with a small effective mass. Most chemical reactions occur on complex, high-dimensional PES that cannot be treated analytically and pose the added challenge of choosing a good CV. We study the influence of that choice and find that, while the reaction free energy is largely unaffected, Δ F RP ‡ is quite sensitive. [ABSTRACT FROM AUTHOR]

By using a recently formulated Legendre transform approach to the thermodynamics of charged systems, we explore the general form of the screening length in the Voorn–Overbeek-type theories, which remains valid also in the cases where the entropy of the charged component(s) is not given by the ideal gas form as in the Debye–Hückel theory. The screening length consistent with the non-electrostatic terms in the free energy ansatz for the Flory–Huggins and Voorn–Overbeek type theories, derived from the local curvature properties of the Legendre transform, has distinctly different behavior than the often invoked standard Debye screening length, though it reduces to it in some special cases. [ABSTRACT FROM AUTHOR]

For chemical reactions that occur via the rearrangement of atoms from a configuration about one minimum (reactant, R) of the potential energy surface (PES) to a configuration about another minimum (product, P), an exact relation between the Helmholtz reaction free energy (ΔFRP) and the free-energy profile (FEP) can be derived. Since the FEP assumes a form similar to that of the PES along the minimum energy path between R and P, there is an unfortunate tendency to regard the FEP as the "free-energy" analog of the minimum energy path and consequently to equate ΔFRP to the difference between the values of the FEP at the minima corresponding to R and P. Analytic treatments of one- and two-dimensional models are presented that show how this mistaken idea leads to errors. In effect, treating the FEP by analogy with the minimum energy path neglects the role of entropy. The FEP is a function of a collective variable (CV), which must be chosen to describe the course of the rearrangement consistently with the exact relation between ΔFRP and the FEP. For large systems of common interest, the PES is often so complex that a straightforward way of choosing a CV is lacking. Consequently, one is forced to make an educated guess. A criterion for judging the quality of the guess is proposed and applied to a two-dimensional model. [ABSTRACT FROM AUTHOR]

The construction of the density functional for grand potential is fundamental in understanding a broad range of interesting physical phenomena, such as phase equilibrium, interfacial thermodynamics, and solvation. However, the knowledge of a general functional accurately describing the many-body correlation of molecules is far from complete. Here, we propose a self-consistent construction of the grand potential functional based on the weighted density approximation (WDA) utilizing hierarchical integral equations. Different from our previous study [T. Yagi and H. Sato, J. Chem. Phys. 154, 124113, (2021)], we apply the WDA to the excess Helmholtz free energy functional rather than the bridge functional. To assess the performance of the present functional, we apply it to the solvation thermodynamics of Lennard-Jones fluids. Compared to the modified Benedict–Webb–Rubin equation of state, the present functional qualitatively predicts the liquid–vapor equilibrium. The solvation free energy obtained from the present functional provides a much better agreement with the Monte Carlo simulation result than the hypernetted chain functionals. It constitutes a general starting point for a systematic improvement in the accuracy of the grand potential functional. [ABSTRACT FROM AUTHOR]

In this article, thermodynamic analysis and calculations of the chemical reaction of carbidization of titanium dioxide in the presence of calcium and calcium carbide and only calcium carbide was carried using the first approximation of thermodynamic analysis - "accelerated calculation method". Thermodynamic analysis of the reaction was carried out based on the results of step-by-step calculation of the sign value of the isobaric potential of each reaction for the ranges of temperatures corresponding to each modification of the substances involved in the chemical reaction. [ABSTRACT FROM AUTHOR]

Free energies of a solid surface and a solid–liquid interface play significant roles in thermodynamics. Due to the limited availability of experimental data, computational methods offer effective alternatives for calculating these properties. This study adopts advanced frameworks of the logarithmic mean force dynamics method to present an enhanced sampling approach for the calculation of the free energy at different temperatures. To achieve this, the free energy profile is constructed along with a pre‐established collective variable within the melting transition and cleavage processes. The values of the solid surface and solid–liquid interface free energies are then extrapolated from the excess free energy related to the formation and persistence of the solid surface or the solid–liquid interface. Furthermore, this methodology is employed to calculate the temperature dependence of the free energy measurements for the (100) and (110) surfaces and interfaces of Cu. It is shown that this methodology is robust and readily applicable in contemporary models of atomic interactions and various systems. [ABSTRACT FROM AUTHOR]

All processes involving molecular systems entail a balance between associated enthalpic and entropic changes. Molecular dynamics simulations of the end‐points of a process provide in a straightforward way the enthalpy as an ensemble average. Obtaining absolute entropies is still an open problem and most commonly pathway methods are used to obtain free energy changes and thereafter entropy changes. The kth nearest neighbor (kNN) method has been first proposed as a general method for entropy estimation in the mathematical community 20 years ago. Later, it has been applied to compute conformational, positional–orientational, and hydration entropies of molecules. Programs to compute entropies from molecular ensembles, for example, from molecular dynamics (MD) trajectories, based on the kNN method, are currently available. The kNN method has distinct advantages over traditional methods, namely that it is possible to address high‐dimensional spaces, impossible to treat without loss of resolution or drastic approximations with, for example, histogram‐based methods. Application of the method requires understanding the features of: the kth nearest neighbor method for entropy estimation; the variables relevant to biomolecular and in general molecular processes; the metrics associated with such variables; the practical implementation of the method, including requirements and limitations intrinsic to the method; and the applications for conformational, position/orientation and solvation entropy. Coupling the method with general approximations for the multivariable entropy based on mutual information, it is possible to address high dimensional problems like those involving the conformation of proteins, nucleic acids, binding of molecules and hydration. This article is categorized under:Molecular and Statistical Mechanics > Free Energy MethodsTheoretical and Physical Chemistry > Statistical MechanicsStructure and Mechanism > Computational Biochemistry and Biophysics [ABSTRACT FROM AUTHOR]

The role of organic compounds in atmospheric new particle formation is difficult to disentangle due to the myriad of potentially important oxygenated organic molecules (OOMs) present in the atmosphere. Using state-of-the-art quantum chemical methods, we here employ a novel approach, denoted the "cluster-of-functional-groups" approach, for studying the involvement of OOMs in atmospheric cluster formation. Instead of the usual "trial-and-error" approach of testing the ability of experimentally identified OOMs to form stable clusters with other nucleation precursors, we here study which, and how many, intermolecular interactions are required in a given OOM to form stable clusters. In this manner we can reverse engineer the elusive structure of OOM candidates that might be involved in organic enhanced atmospheric cluster formation. We calculated the binding free energies of all combinations of donor and acceptor organic functional groups to investigate which functional groups most preferentially bind with each other and with other nucleation precursors such as sulfuric acid and bases (ammonia, methyl-, dimethyl- and trimethylamine). We find that multiple carboxyl groups lead to substantially more stable clusters compared to all other combinations of functional groups. Employing cluster dynamics simulations, we investigate how a hypothetically OOM composed of multiple carboxyl groups can stabilize sulfuric acid-base clusters and provide recommendations for potential atmospheric multi-carboxylic acid tracer compounds that should be explicitly studied in the future. The presented "cluster-of-functional-groups" approach is generally applicable and can be employed in many other applications, such as ion-induced nucleation and potentially in elucidating the structural patterns in molecules that facilitate ice nucleation. [ABSTRACT FROM AUTHOR]

The present work aims to investigate the structural and thermodynamic properties of homogenous tetragonal Cu2ZnSnS4 (CZTS) absorber material in Kesterite phase using first-principle calculations based on density functional theory (DFT). This approach requires only knowledge of the atomic species and crystal structure to predict several physical properties of materials. The Quantum Espresso code within the Ultra Soft pseudopotentials (USPP) and the local density approximation (LDA) were used in the calculations. Equilibrium unit cell volumes, bulk modulus, as well as the pressure derivative of the bulk modulus are predicted. In addition, several thermodynamic properties, especially: the Debye's vibrational energy, the vibrational free energy, the vibrational entropy, and the constant volume heat capacity at different temperatures T of Cu2ZnSnS4 material are calculated and discussed. Our study shows that the vibrational energy, the entropy and the constant volume heat capacity increase with increasing temperature, while the vibrational free energy decreases monotonously with the increase of temperature. [ABSTRACT FROM AUTHOR]

Serine hydroxymethyltransferase 2 (SHMT2) has garnered significant attention as a critical catalytic regulator of the serine/glycine pathway in the one-carbon metabolism of cancer cells. Despite its potential as an anti-cancer target, only a limited number of inhibitors have been identified so far. In this study, we employed seven different scoring functions and skeleton clustering to screen the ChemDiv database for 38 compounds, 20 of which originate from the same skeleton structure. The most significant residues from SHMT2 and chemical groups from the inhibitors were identified using ASGBIE (Alanine Scanning with Generalized Born model and Interaction Entropy), and the binding energy of each residue was quantitatively determined, revealing the essential features of the protein–inhibitor interaction. The two most important contributing residues are TYR105 and TYR106 of the B chain followed by LEU166 and ARG425 of the A chain. The findings will be greatly helpful in developing a thorough comprehension of the binding mechanisms involved in drug–SHMT2 interactions and offer valuable direction for designing more potent inhibitors. [ABSTRACT FROM AUTHOR]

Due to the similarity of host–guest complexes and protein–ligand and protein–protein assemblies, computational tools for protein–drug complexes are commonly applied in host–guest binding. One of the methods with the highest popularity is the end-point free energy technique, which estimates the binding affinity with gas-phase and solvation contributions extracted from simplified end-point sampling. Our series papers on a set of carboxylated-pillararene host–guest complexes have proven with solid numerical evidence that standard end-point techniques are practically useless in host–guest binding, but alterations, such as slightly increasing interior dielectric constant in post-processing calculation and shifting to the multi-trajectory realization in conformational sampling, could better the situation and pull the end-point method back to the pool of usable tools. Also, the force-field selection plays a critical role, as it determines the sampled region in the conformational space. In the current work, we continue the efforts to explore potentially promising end-point modifications in host–guest binding and further extend the sampling time to an unprecedent length. Specifically, we comprehensively benchmarked the shift from the original MM description to QM Hamiltonians in post-processing the popular single-trajectory sampling. Two critical settings in the multi-scale QM/GBSA regime are the selections of the QM Hamiltonian and the implicit-solvent model, and a scan of combinations of popular semi-empirical QM Hamiltonians and GB models is performed. The multi-scale QM/GBSA treatment is further combined with the three-trajectory sampling protocol, introducing a further advanced modification. The sampling lengths in the host–guest complex, solvated guest and solvated host ensembles are extended to 500 ns, 500 ns and 12,000 ns. As a result, the sampling quality in end-point calculations is unprecedently high, enabling us to draw conclusive pictures of investigated forms of modified end-point free energy methods. Numerical results suggest that the shift to the QM Hamiltonian does not better the situation in the popular single-trajectory regime, but noticeable improvements are observed in the three-trajectory sampling regime, especially for the DFTB/GBSA parameter combination (either DFTB2 or its third-order extension), the quality metrics of which reach an unprecedently high level and surpass existing predictions (including costly alchemical transformations) on this dataset, hinting on the applicability of the advanced three-trajectory QM/GBSA end-point modification for host–guest complexes. [ABSTRACT FROM AUTHOR]

The removal and detection of ciprofloxacin (CPX) as an emerging environmental contaminant and a medicine are of great importance. In this respect, the performance of carbon nanocone (CNC) as a sensing material and an adsorbent for CPX was investigated by infrared-red (IR), frontier molecular orbital (FMO), and natural bond orbital (NBO) computations. The calculated adsorption energies, Gibbs free energy changes, enthalpy changes, and thermodynamic constants showed that CPX interaction with CNC was experimentally feasible, exothermic, and spontaneous. The NBO results indicated that CPX interaction with CNC was physisorption and no bond was created among the adsorbent and adsorbate. Moreover, findings on the effect of the temperature indicated that the adsorption process was more favorable at lower temperatures. The computed bandgap values showed that when CPX was adsorbed on the surface of CNC, the bandgap of CNC experienced a sharp decline (-26%) from 6.880 to 5.040 (eV). Hence, this nanostructure is a suitable sensing material for the development of novel electrochemical sensors for the determination of CPX. [ABSTRACT FROM AUTHOR]

Papain-like protease (PLpro), a non-structural protein encoded by SARS-CoV-2, is an important therapeutic target. Regions 1 and 5 of an existing drug, GRL0617, can be optimized to produce cooperativity with PLpro binding, resulting in stronger binding affinity. This work investigated the origin of the cooperativity using molecular dynamics simulations combined with the interaction entropy (IE) method. The regions' improvement exhibits cooperativity by calculating the binding free energies between the complex of PLpro-inhibitor. The thermodynamic integration method further verified the cooperativity generated in the drug improvement. To further determine the specific source of cooperativity, enthalpy and entropy in the complexes were calculated using molecular mechanics/generalized Born surface area and IE. The results show that the entropic change is an important contributor to the cooperativity. Our study also identified residues P248, Q269, and T301 that play a significant role in cooperativity. The optimization of the inhibitor stabilizes these residues and minimizes the entropic loss, and the cooperativity observed in the binding free energy can be attributed to the change in the entropic contribution of these residues. Based on our research, the application of cooperativity can facilitate drug optimization, and provide theoretical ideas for drug development that leverage cooperativity by reducing the contribution of entropy through multi-locus binding. [ABSTRACT FROM AUTHOR]

Crystal structure prediction is a central problem of crystallography and materials science, which until mid-2000s was considered intractable. Several methods, based on either energy landscape exploration or, more commonly, global optimization, largely solved this problem and enabled fully non-empirical computational materials discovery. A major shortcoming is that, to avoid expensive calculations of the entropy, crystal structure prediction was done at zero Kelvin, reducing to the search for the global minimum of the enthalpy rather than the free energy. As a consequence, high-temperature phases (especially those which are not quenchable to zero temperature) could be missed. Here we develop an accurate and affordable solution, enabling crystal structure prediction at finite temperatures. Structure relaxation and fully anharmonic free energy calculations are done by molecular dynamics with a forcefield (which can be anything from a parametric forcefield for simpler cases to a trained on-the-fly machine learning interatomic potential), the errors of which are corrected using thermodynamic perturbation theory to yield accurate results with full ab initio accuracy. We illustrate this method by applications to metals (probing the P–T phase diagram of Al and Fe), a refractory covalent solid (WB), an Earth-forming silicate MgSiO3 (at pressures and temperatures of the Earth's lower mantle), and ceramic oxide HfO2. [ABSTRACT FROM AUTHOR]

We compare several different methods to quantify the uncertainty of binding parameters estimated from isothermal titration calorimetry data: the asymptotic standard error from maximum likelihood estimation, error propagation based on a first-order Taylor series expansion, and the Bayesian credible interval. When the methods are applied to simulated experiments and to measurements of Mg(II) binding to EDTA, the asymptotic standard error underestimates the uncertainty in the free energy and enthalpy of binding. Error propagation overestimates the uncertainty for both quantities, except in the simulations, where it underestimates the uncertainty of enthalpy for confidence intervals less than 70%. In both datasets, Bayesian credible intervals are much closer to observed confidence intervals. [ABSTRACT FROM AUTHOR]

Recently, protein tyrosine phosphatase 1B (PTP1B) inhibitors have become the frontier as possible targeting for anti-cancer and antidiabetic drugs. The contemporary observe represents a pc assisted version to investigate the importance of precise residues within the binding web site of PTP1B with numerous Sanggenon derivatives remoted from nature. Molecular dynamics (MD) simulations were performed to estimate the dynamics of the complexes, and absolute binding unfastened energies have been calculated with exclusive additives, and carried out through the usage of the Molecular Mechanics-Poisson-Boltzmann floor region (MM-PB/SA) and Generalized Born surface vicinity (MM-GB/SA) strategies. The effects show that the expected free energies of the complexes are normally constant with the available experimental statistics. MM/GBSA free energy decomposition analysis shows that the residues Asp29, Arg24, Met258, and, Arg254 in the second active site in PTP1B are crucial for the excessive selectivity of the inhibitors. [ABSTRACT FROM AUTHOR]

This work determines the phase stabilities and point defect energetics of TiSi2 and TiGe2 allotropes using density functional theory. The primary focus is on the C49 and C54 allotropes, which compete during TiSi2 phase formation. It is found that the ground state structure for TiGe2 is the C54 allotrope, desirable for its low sheet resistance, while the less desirable, higher resistance C49 allotrope forms the ground state structure of TiSi2. A first attempt to understand the Ge atom's role in lowering the enthalpy of formation for the C54 structure is made from the perspective of the extended Born model. Charge density differences, the density of states, and Bader charge analysis show that these systems are predominantly ionically bonded, with the Ge atoms introducing additional covalent bond stability for the C54 allotrope. It is known that higher temperatures favor C54 formation in TiSi2. Helmholtz free energy calculations for TiSi2 suggest that the vibrational free energy does not drive the system to the C54 phase. The formation energies of certain point defects within the C49 structure of TiSi2 are less than 1 eV, which is consistent with experiments that show high defect concentrations. Thus, the driving force for C54 formation at higher temperatures may be related to the high defect concentration in the C49 allotrope. [ABSTRACT FROM AUTHOR]

Transport of ions through liquid–liquid interfaces is of fundamental importance to a wide variety of applications. However, since it is quite challenging for experimentalists to directly and selectively observe molecules at the interfaces, microscopic mechanisms of ion transport have been largely presumed from kinetic information. This Perspective illustrates recent examples that molecular dynamics simulations with proper free energy surfaces clarified mechanistic pictures of ion transport. The key is a proper choice of coordinates and defining/calculating free energy surfaces in multidimensional space. Once the free energy surfaces for realistic systems are available, they naturally provide new insight into the ion transport in unprecedented details, including water finger, transient ion pairing, and electron transfer. [ABSTRACT FROM AUTHOR]

In this study, equilibrium conditions and kinetics of sorption of Cu2+, Zn2+, Cd2+ and Pb2+ ions with Dowex MAC-3 (carboxyl group, H+) cationite were studied, thermodynamic quantities were calculated based on kinetic parameters. It was noted that the kinetics of the processes at the selected concentrations are under internal diffusion control. Sorption isotherms were established, Langmuir and Freundlich models were proposed. In all cases, the selectivity is governed by the enthalpy factor with heat release and entropy reduction. The variation of parameters such as activation energy of sorption, free energy, activation entropy and diffusion coefficients varies due to various factors. In the calculation of thermodynamic parameters, the ideality of the ionic phase was determined, in other words, the activity coefficients of the sorbed ions in the ionic phase were not taken into account. [ABSTRACT FROM AUTHOR]

The most important mechanisms in the blood pressure regulation, fluid volume and sodium-potassium balance in humans is the renin-angiotensin-aldosterone system (RAAS). This regulatory pathway plays a critical role in modulating cardiac function and vascular tone. An alteration in any of the molecules that make up this system (RAAS) could contribute to the development of arterial hypertension. In this important mechanisms, the neutral endopeptidase, also called Neprilysin (NEP) is the main enzyme for the degradation of natriuretic, therefore, it is essential proteins in controlling blood pressure. In this work, we have used docking methodology, molecular dynamics simulationa and free energy calculations method (MM-PBSA), to comprehensively evaluate the inhibitory behavior of some ligands obteined from consulted literature. The principal results obtained shown these ligands were adequately oriented in the NEP pocket. The Lig783, Lig2177, and Lig3444 compounds were those with better dynamic behavior. The energetic components that contribute to the complex's stability are the electrostatic and Van der Waals components; however, when the ADME-Tox properties were analyzed, we conclude that the best possible anti-hypertensive candidate are Lig783 and Lig3444. [ABSTRACT FROM AUTHOR]

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The study of the surface thermodynamic properties of solid materials is primordial for the determination of the dispersive surface energy, polar enthalpy of adsorption and Lewis's acid base properties of solid particles. The inverse gas chromatography technique (IGC) at infinite dilution is the best surface technique for the determination of the surface physicochemical properties of materials. (1) Background: This paper was devoted to studying the surface properties of solid materials, such as alumina, titania and silica particles, using the IGC technique. (2) Methods: Different methods and molecular models, such as the spherical, cylindrical, Van der Waals, Redlich–Kwong, Kiselev and geometric models, were used to determine the London dispersive surface energy of solid surfaces. The Hamieh model was also used and highlighted the thermal effect on the surface area of solvents. (3) Results: The variations of the dispersive surface energy and the free energy of adsorption were determined for solid particles as a function of the temperature, as well as their Lewis's acid base constants. Alumina surfaces were proved to exhibit a strong Lewis amphoteric character three times more basic than acidic, titanium dioxide more strongly basic than acidic and silica surface exhibited the stronger acidity. (4) Conclusions: The new methodology, based on the Hamieh model, gave the more accurate results of the physicochemical properties of the particle surfaces. [ABSTRACT FROM AUTHOR]

Tools to predict vapor–liquid phase equilibria are indispensable for the conceptualization and design of separation processes. Modified separation of cohesive energy density (MOSCED) is a solubility-parameter-based method parameterized to make accurate predictions of the limiting activity coefficient. As a solubility-parameter-based method, MOSCED can not only make quantitative predictions, but can shed light on the underlying intermolecular interactions. In the present study, we demonstrated the ability of MOSCED to correlate the enthalpy of vaporization and vapor pressure at a specific temperature using multiple linear regression. With this addition, MOSCED is able to predict vapor–liquid phase equilibria in the absence of reference data. This was demonstrated for the prediction of the Henry's constant and solvation free energy of organic solutes in water, which was found to be superior to mod-UNIFAC. In addition to being able to make phase equilibrium predictions, the ability to correlate the enthalpy of vaporization and vapor pressure offers the opportunity to include additional properties in the regression of the MOSCED parameters. Given this success, we additionally attempted to correlate a wide range of physical properties using a similar expression. While, in some cases, the results were reasonable, they were inferior to the correlations of the enthalpy of vaporization and vapor pressure. Future efforts will be needed to improve the correlations. [ABSTRACT FROM AUTHOR]

Background: Pesticide contamination to water, continues to raise ecotoxicological and human concerns. Studying the application of green adsorbents for removing pesticides from water can significantly reduce ecotoxicological impacts and sustain reclamation of water bodies. Results: The current study investigated the adsorption capacity of MgO/Fe3O4 modified coconut shell biochar (MCSB) towards Atrazine removal in water. The prepared adsorbents were structurally constricted and obtained relative amount of mesopore spaces filled by nanoparticles which equally provided active occupancy/binding sites for Atrazine molecule deposition. Equilibrium isotherm studies under temperature regimes of 300 K, 318 K and 328 K were best described by the Freundlich isotherm (R2 = 0.95–0.97) with highest adsorption capacity corresponding to the highest temperature range (328 K) at (KF = 9.60 L mg−1). The kinetics modelling was best fitted to the pseudo second-order kinetic (R2 = 0.90–0.98) reaction pathways revealing that Atrazine uptake and removal occurred majorly over non-homogenous surfaces and high influence of surface functional groups in the process. Atrazine uptake by the adsorbent were mostly efficient within pH ranges of 2–6. Thermodynamics values of free energy ΔG° were negative ranging (ΔG° = − 27.50 to − 29.77 kJ mol−1) across the varying reaction temperature indicating an exothermic reaction, while enthalpy (ΔH°) (34.59 kJ mol) and entropy (ΔS°) (90.88 JK−1/mol) values were positive revealing a degree of spontaneity which facilitated Atrazine uptake. The adsorbents regeneration capacities over five cycles were observed to decrease proportionally with maximum yields up to 50–60%. Optimization of the adsorption condition by response surface modelling (RSM) and Central Composite Design (CCD) could reveal optimum conditions for Atrazine removal through interaction of different variables at pH = 12, adsorbate initial concentration at 12 mg L−1, adsorbate dosage at 0.5 g and reaction temperature at 54 °C. The overall mechanisms of the adsorption could be contributed by availability of surface functional groups on the MCSB surface through increase in hydrophilicity facilitating easy Atrazine molecule attachment via hydrogen bonding and improved surface complexation. Conclusions: The as-synthesized MCSB adsorbent could uptake and remove Atrazine in water. A high pH, low concentration, low adsorbent dosage and high reaction temperature could be optimized conditions to attain highest Atrazine removal by the synthesized adsorbent. [ABSTRACT FROM AUTHOR]

Updated Abraham model correlations are reported for the transfer of organic solutes and inorganic gases to a polydimethylsiloxane coating from both water and the gas phase based on published experimental data for more than 220 different compounds. The derived mathematical expressions back-calculate the observed partitioning behavior to within standard deviations of the residuals of 0.206 and 0.176 log units, respectively. [ABSTRACT FROM AUTHOR]

We explore and show the usefulness of the density of states function for computing vibrational free energies and free energy differences between small systems. Therefore, we compare this density of states integration method (DSI) to more established schemes such as Bennett's Acceptance Ratio method (BAR), the Normal Mode Analysis (NMA), and the Quasiharmonic Analysis (QHA). The strengths and shortcomings of all methods are highlighted with three numerical examples. Furthermore, the free energy of the ionization of ammonia and the mutation from serine to cysteine are computed using extensive ab initio molecular dynamics simulations. We conclude that DSI improves upon the other frequency-based methods (NMA and QHA) regarding the treatment of anharmonicity and yielding results comparable to BAR in all cases without the need for alchemical transformations. Low-frequency modes lead to larger errors indicating that long simulation times might be required for larger systems. In addition, we introduce the use of DSI for the localization of the vibrational free energy to specific atoms or residues, leading to insights into the underlying process, a unique feature that is only offered by this method. [ABSTRACT FROM AUTHOR]

A quantitative continuum model for oxide precipitation in silicon is presented that accounts for vacancy absorption and shape change as mechanisms of precipitate stress relief. All model parameters except one, the Si/SiO2 interface free energy, are fixed at values established in prior studies of microdefect formation. The interface free energy is described by an 8-parameter function, whose functional form and dependencies were based on an analysis of electronic structure calculations of small oxide cluster thermodynamics. The interface energy function parameters are regressed, using global optimization, to an experimental benchmark consisting of 13 wafer thermal anneals, with different temperature-time histories and resulting in widely varying measured final oxide precipitate densities. We demonstrate that the model is able to capture the benchmark features well with multiple parameter combinations and that additional constraints are required to fully specify a unique solution. We also show that a simple, single-parameter, constant interface free energy model cannot fully capture the diverse experimental benchmark, highlighting the complexity of oxide precipitation. The precipitation model is used to analyze the mechanisms responsible for several features of oxide nucleation and growth during wafer annealing. [ABSTRACT FROM AUTHOR]

We propose a Reweighted Partial Path (RPP) method to compute free energy profiles for diffusive processes in single Transition Interface Sampling (TIS) or Forward Flux Sampling (FFS) simulations. The method employs a partial path reweighting strategy, based on the memory loss assumption for diffusive systems, to derive the equilibrium distribution of states along a chosen order parameter from TIS or FFS trajectories. No additional calculations such as reverse TIS or umbrella sampling are required. The application of the RPP method is demonstrated by calculating the nucleation free energy of early-stage Cu precipitates in a dilute Fe-Cu alloy. [ABSTRACT FROM AUTHOR]

Phase transition and dielectric tunability of (011) epitaxial Ba0.6Sr0.4TiO3 are modeled using a thermodynamic phenomenological approach. Relative stability of the ferroelectric phases is computed using an improved thermodynamic model and three sets of free energy coefficients. Room-temperature bias field dependence of dielectric constants for a series of anisotropically strained films is calculated and compared with relevant experimental data in the literature. We show that the dielectric tunability can be optimized by manipulating structural transitions via the epitaxial strain. [ABSTRACT FROM AUTHOR]

We introduce a molecular simulation method to compute the interfacial properties of model systems within the isothermal-isobaric ensemble. We use a free-energy-based approach in which Monte Carlo simulations are employed to obtain an interface potential associated with the growth of a fluid film from a solid substrate. The general method is implemented within "spreading" and "drying" frameworks. The interface potentials that emerge from these calculations provide direct access to spreading and drying coefficients. These macroscopic properties are then used to compute the liquid-vapor surface tension and the contact angle of a liquid droplet in contact with the substrate. The isothermal-isobaric ensemble provides a means to change the thickness of the fluid film adjacent to the substrate by modifying the volume of the simulation box. Molecular insertions and removals are not necessary. We introduce a framework for performing local volume change moves wherein one attempts to modify the density of a narrow region of the simulation box. We show that such moves improve the sampling efficiency of inhomogeneous systems. The approach is applied to a model system consisting of a monatomic Lennard-Jones fluid in the vicinity of a structureless substrate. Results are provided for direct spreading and drying interface potential calculations at several temperatures and substrate strengths. Expanded ensemble techniques are used to evaluate interfacial properties over a wide range of temperatures and substrate strengths. The results obtained using the isothermal-isobaric approach are compared with those previously obtained via a grand canonical approach. [ABSTRACT FROM AUTHOR]

Insulin-dimer dissociation is an essential biochemical process required for the activity of the hormone. We investigate this dissociation process at the molecular level in water and at the same time, in 5% and 10% water-ethanol mixtures. We compute the free energy surface of the protein dissociation processes by employing biased molecular dynamics simulation. In the presence of ethanol (EtOH), we observe a marked lowering in the free energy barrier of activation of dimer dissociation from that in the neat water, by as much as ∼50%, even in the 5% water-ethanol solution. In addition, ethanol is found to induce significant changes in the dissociation pathway. We extract the most probable conformations of the intermediate states along the minimum energy pathway in the case of all the three concentrations (EtOH mole fractions 0, 5, and 10). We explore the change in microscopic structures that occur in the presence of ethanol. Interestingly, we discover a stable intermediate state in the water-ethanol binary mixture where the centers of the monomers are separated by about 3 nm and the contact order parameter is close to zero. This intermediate is stabilized by the wetting of the interface between the two monomers by the preferential distribution of ethanol and water molecules. This wetting serves to reduce the free energy barrier significantly and thus results in an increase in the rate of dimer dissociation. We also analyze the solvation of the two monomers during the dissociation and both the proteins' departure from the native state configuration to obtain valuable insights into the dimer dissociation processes. [ABSTRACT FROM AUTHOR]

We formulate a new theory for how caging constraints in glass-forming liquids at a surface or interface are modified and then spatially transferred, in a layer-by-layer bootstrapped manner, into the film interior in the context of the dynamic free energy concept of the Nonlinear Langevin Equation (NLE) theory approach. The dynamic free energy at any mean location (cage center) involves contributions from two adjacent layers where confining forces are not the same. At the most fundamental level of the theory, the caging component of the dynamic free energy varies essentially exponentially with distance from the interface, saturating deep enough into the film with a correlation length of modest size and weak sensitivity to the thermodynamic state. This imparts a roughly exponential spatial variation of all the key features of the dynamic free energy required to compute gradients of dynamical quantities including the localization length, jump distance, cage barrier, collective elastic barrier, and alpha relaxation time. The spatial gradients are entirely of dynamical, not structural or thermodynamic, origin. The theory is implemented for the hard sphere fluid and diverse interfaces which can be a vapor, a rough pinned particle solid, a vibrating (softened) pinned particle solid, or a smooth hard wall. Their basic description at the level of the spatially heterogeneous dynamic free energy is identical, with the crucial difference arising from the first layer where dynamical constraints can be weakened, softened, or hardly changed depending on the specific interface. Numerical calculations establish the spatial dependence and fluid volume fraction sensitivity of the key dynamical property gradients for five different model interfaces. A comparison of the theoretical predictions for the dynamic localization length and glassy modulus with simulations and experiments for systems with a vapor interface reveals good agreement. The present advance sets the stage for using the Elastically Collective NLE theory to make quantitative predictions for the alpha relaxation time gradient, decoupling phenomena, Tg gradient, and many film-averaged properties of both model and experimental (colloids, molecules, and polymers) systems with diverse interfaces and chemical makeup. [ABSTRACT FROM AUTHOR]

Free energy calculations for chemical reactions with a steep energy barrier require well defined reaction coordinates (RCs). However, when multiple parallel channels exist along selected RC, the application of conventional enhanced samplings is difficult to generate correct sampling within limited simulation time and thus cannot give correct prediction about the favorable pathways, the relative stability of multiple products or intermediates. Here, we implement the selective integrated tempering sampling (SITS) method with quantum mechanical and molecular mechanical (QM/MM) potential to investigate the chemical reactions in solution. The combined SITS-QM/MM scheme is used to identify possible reaction paths, intermediate and product states, and the free energy profiles for the different reaction paths. Two double proton transfer reactions were studied to validate the implemented method and simulation protocol, from which the independent and correlated proton transfer processes are identified in two representative systems, respectively. This protocol can be generalized to various kinds of chemical reactions for both academic studies and industry applications, such as in exploration and optimization of potential reactions in DNA encoded compound library and halogen or deuterium substitution of the hit discovery and lead optimization stages of drug design via providing a better understanding of the reaction mechanism along the designed chemical reaction pathways. [ABSTRACT FROM AUTHOR]

Within scaled-particle theory, we construct an equation of state (EOS) for hard-disk mixtures by making use of an additional scaled-particle variable which weighs the densities of the different components by its radii to the power χ. This allows us to simultaneously respect exact results pertaining to the cases of a large particle or a point particle being added to the mixture. In the limit χ → 2, the mixture EOS of Santos et al. [Mol. Phys. 96, 1 (1999)] is recovered, while the limit χ → 0 yields the accurate expression for the interfacial free energy of Martin et al. [J. Chem. Phys. 149, 084701 (2018)]. From the low-density limit of the EOS, the value χ ≈ 0.8 is extracted, which is shown to yield a mixture EOS that is significantly more accurate than the expressions due to Santos et al. and Martin et al. In particular, the systematic deviation inherent to these prior results is remedied. [ABSTRACT FROM AUTHOR]