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Biochars are an exciting class of environmental materials with a wide range of applications, including carbon storage and sequestration, soil enhancement, and pollution remediation. However, the limited knowledge of their molecular structures and compositions and the lack of comprehensive understanding of the relationship between these structures and biochars' diverse functionality, is hindering advancements in their development. In this work, we further advance the approach, first introduced by Wood et al. (2023), to constructing biochar molecular models; and now include control of microporosity (pores ≤ 2 nm size) within the developed models. We construct biochar models representative of woody biochars which are experimentally produced at 600–650 ° C highest heating temperatures. Our models reproduce experimental H/C and O/C atomic ratios, percentage aromatic carbon, true density, cumulative porosity, and pore size distribution. The development of microporous biochar molecular models allows us to identify the importance of chemical structures involved in the assembly of biochar materials, and describe the relationship between these structures and obtained micropores. To facilitate other researchers integrating our approach into their work, we detail the steps taken, including the tests and reasons for each decision, in the construction of the biochar models. Furthermore, we share our developed molecular models in a format that can be easily integrated into other group's work in the form of molecular dynamics simulations. • Molecular models of biochar with controlled pore volumes and pore size distribution. • Models truthful to experimental H/C, O/C, aromaticity, true density and microporosity. • Identification of structural moieties within biochar – key to supporting micropores. [ABSTRACT FROM AUTHOR]

[Display omitted] • Non-idealities at the solid/liquid interface obtained from molecular simulations. • Molecular dynamics simulations maintain a constant solution composition. • NaCl(aq) at graphite and at NaCl(s) surfaces displays asymmetric ion adsorption. • Asymmetric adsorption induces an electric potential at the solid/liquid interface. Solid/liquid interfaces control various processes of technological relevance in the process industry and many fundamental physicochemical phenomena. This work examines the link between the atomistic description of mass transfer at solid/liquid interfaces out of equilibrium and constitutive mass transfer equations which are typically used to model these processes at the mesoscale. In our analyses we discuss the microscopic inconsistencies apparent in simplified models of mass transfer whenever non-idealities dominate the liquid phase in the proximity of solid/liquid interfaces. Using C μ MD – a molecular simulation technique to investigate out-of-equilibrium, concentration-driven processes with pseudo open-boundary conditions – we outline a strategy to capture and quantify non-idealities induced by specific interactions between the solid surface and molecules in the fluid phase. We demonstrate our approach by studying electrolyte solutions in technologically important, multi-component systems where the introduction of a solid/liquid interface induces substantial deviations in the composition and electrochemical properties locally compared to the bulk fluid phase. To this aim, we analyse NaCl(aq) solutions in contact with (i) the graphite basal surface and (ii) {100} NaCl(s) crystalline surfaces. We uncover the tendency of the sodium cation to preferentially adsorb at the surfaces considered, which induces local violations of electroneutrality that leads to the emergence of an electric potential in the fluid phase at the solid/liquid interface. [ABSTRACT FROM AUTHOR]

Abstract: For years, conventional drug design at G-protein coupled receptors (GPCRs) has mainly focused on the inhibition of a single receptor at a usually well-defined ligand-binding site. The recent discovery of more and more physiologically relevant GPCR dimers/oligomers suggests that selectively targeting these complexes or designing small molecules that inhibit receptor–receptor interactions might provide new opportunities for novel drug discovery. To uncover the fundamental mechanisms and dynamics governing GPCR dimerization/oligomerization, it is crucial to understand the dynamic process of receptor–receptor association, and to identify regions that are suitable for selective drug binding. This minireview highlights current progress in the development of increasingly accurate dynamic molecular models of GPCR oligomers based on structural, biochemical, and biophysical information that has recently appeared in the literature. In view of this new information, there has never been a more exciting time for computational research into GPCRs than at present. Information-driven modern molecular models of GPCR complexes are expected to efficiently guide the rational design of GPCR oligomer-specific drugs, possibly allowing researchers to reach for the high-hanging fruits in GPCR drug discovery, i.e. more potent and selective drugs for efficient therapeutic interventions. [Copyright &y& Elsevier]

Abstract: This report presents evidence that ibuprofen interacts with red cell membranes as follows: a) in scanning electron microscopy (SEM) studies on human erythrocytes induced shape changes at a concentration as low as 10μM; b) in isolated unsealed human erythrocyte membranes (IUM) induced mild increase in the water content or in their molecular dynamics at the hydrophobic–hydrophilic interphase, while a corresponding ordering decrease at the deep phospholipids acyl chain level; c) at physiological temperature (37°C), 300μM ibuprofen induced a significant increase in the generalized polarization (GP) of dimyristoylphosphatidylcholine (DMPC) large unilamellar vesicles (LUV), an indication that ibuprofen molecules locate in the head polar group region of DMPC; d) X-ray diffraction studies showed that ibuprofen concentrations≥300μM induced increasing structural perturbation to DMPC bilayers; e) differential scanning calorimetry (DSC) data showed that ibuprofen was able to alter the cooperativity of DMPC phase transition in a concentration-dependent manner, to destabilize the gel phase and that ibuprofen did not significantly perturb the organization of the lipid hydrocarbon chains. Additionally, the effect on the viability of both human promyelocytic leukemia HL-60 and human cervical carcinoma HeLa cells was studied. [Copyright &y& Elsevier]

Abstract In this work two Sodium Dodecyl Sulphate (SDS) molecular models are proposed; one based on the Explicit-Atom (EA) approach while the other on the United-Atom (UA) approach. A SDS aqueous solution was simulated using the TIP4P/ ε potential for water. With the EA model the micellar aggregate spent less than 1 ns of simulation time to be formed. This is a quite low simulation time compared to the 23 ns spent by existing SDS models to attain the same micellar formation. When both proposed models are compared, micellar formation from EA model is 10 times faster than the UA model. The time reduction is due to the implementation of two repulsive sites in the carbon atoms on the hydrophobic tails. To validate the models, density, radial distribution functions, radius of gyration and shear viscosity were calculated; results were in good agreement with those reported in literature. Graphical Abstract Highlights • Two molecular models of the SDS surfactant in aqueous solutions are proposed. • A 95% in the micelle time formation by using molecular simulation is attained. • The structure of the micelle formed agrees with reported works. • The flow curve exhibits a well-defined Newtonian and a viscous thinning area. [ABSTRACT FROM AUTHOR]

Abstract This study was aimed at elucidating the molecular mechanisms of the interaction of the antitumor alkylphospholipid drug miltefosine with human erythrocytes (RBC) and molecular models of its membrane. The latter consisted of bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), representative of phospholipid classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. X-ray results showed that the drug interacted with DMPC multilayers; however, no effects on DMPE were detected. The experimental findings obtained by differential scanning calorimetry (DSC) indicated that miltefosine altered the thermotropic behavior of both DMPC and DMPE vesicles. Fluorescence spectroscopy evidenced an increase in the fluidity of DMPC vesicles and human erythrocyte membranes. Scanning electron microscopy (SEM) observations on human erythrocytes showed that miltefosine induced morphological alterations to RBC from its normal biconcave to an echinocyte type of shape. These results confirm that miltefosine interacts with the outer moiety of the human erythrocyte membrane affecting the cell morphology. Graphical abstract Unlabelled Image Highlights • Miltefosine interacted with the human erythrocyte membrane. • The drug increased the fluidity of human erythrocyte ghosts. • Miltefosine changed the shape of erythrocytes forming echinocytes. • Effects on erythrocytes occurred with very low drug concentrations. [ABSTRACT FROM AUTHOR]

The sensitivity of collision cascades simulations to the Two-Temperature Model main parameters is investigated by performing an extensive statistical study both in Si and Ge materials. The purpose is to identify the parameters of the Two-Temperature Model whose impact is the most significant on the cascades properties and to discuss the physical role of each parameter. We demonstrate that the electronic stopping power and electron–phonon coupling have a drastic impact both in Si and Ge but that these two parameters act differently on those two materials due to their distinct thermal properties. We show that the formation of thermal spikes and therefore of amorphous pockets is sensitive to the electronic specific heat. The effects are again very distinct in Si and in Ge. The influence of both the threshold velocity for the stopping power and the electron–phonon coupling activation time are found to be negligible at the considered energies. [ABSTRACT FROM AUTHOR]

Carbon deposition occurs when Dimethyl ether (DME) fuel is used for SOFC, leading to battery degradation. In order to study the effect of water addition on carbon deposition, this work used reactive force field molecular dynamics (Reaxff MD) to simulate the process of carbon deposition with or without water addition, and analyze its anti-carbon deposition mechanism on nickel-based anode. It is found that the number of carbon atoms on nickel can be effectively reduced by mixing water with fuel. As the H 2 O/DME ratio increases, there are fewer carbon atoms on the nickel anode. And there are two main ways for water molecules to resist carbon deposition. First is that the OH group generated by decomposition of water molecules at high temperature reacts with CH component to form aldehyde group, which reduces the formation of carbon deposition precursor. The other is that the increase of water molecules introduces more oxygen atoms into the system, and the carbon atoms formed by DME molecules combine with oxygen atoms to form CO, thus reducing carbon deposition. This study is helpful to promote the industrialization of DME as SOFC fuel. • The anti-carbon deposition mechanism of water is studied by ReaxFF MD. • The carbon deposition can be effectively reduced by mixing water with fuel. • The OH group reacts with CH component to reduce carbon deposition. • The carbon atoms combine with oxygen atoms to reduce carbon deposition. [ABSTRACT FROM AUTHOR]

In this paper, the validity and accuracy of three interatomic potentials and the continuum shell model of Ghaffari and Sauer [1] are investigated. The mechanical behavior of single-layered graphene sheets (SLGSs) under uniaxial stretching, biaxial stretching and pure bending is studied for this comparison. The validity of the molecular and continuum models is assessed by direct comparison with density functional theory (DFT) data available in the literature. The molecular simulations are carried out employing the MM3, Tersoff and REBO + LJ potentials. The continuum formulation uses an anisotropic hyperelastic material model in the framework of the geometrically exact Kirchhoff-Love shell theory and isogeometric finite elements. Results from the continuum model are in good agreement with those from DFT. The results from the MM3 potential agree well up to the point of material instability, whereas those from the REBO + LJ and Tersoff potentials agree only for small deformations. Only the Tersoff potential is found to yield auxetic response in SLGSs under uniaxial stretch. Additionally, the transverse vibration frequencies of a pre-stretched graphene sheet and a carbon nanocone are obtained using the continuum model and molecular simulations with the MM3 potential. The variations of the frequencies from these approaches agree within an error of ≈ 5 %. Image 1 [ABSTRACT FROM AUTHOR]

Abstract: Liquid MgSiO3 is a model for the Earth’s magma ocean and of remnant melt present near the core–mantle boundary. Here, models for molten MgSiO3 are computed employing empirical potential molecular dynamics (EPMD) and results are compared to published results including two EPMD studies and three first-principles molecular dynamics (FPMD) models and to laboratory data. The EPMD results derived from the Oganov (OG) potential come closest to the density of MgSiO3 liquid at the 1-bar melting point inferred from the melting curve. At higher P, EPMD densities calculated from the OG potential and FPMD broadly match shock wave studies, with the OG potential yielding the better comparison. Matsui (M) potential results deviate from other studies above ∼50GPa. Overall, results based on the OG potential compare best to experimental densities over the P–T range of the mantle. Isothermally, upon increasing P the mean coordination numbers () of oxygen around Si and Mg monotonically increase with pressure. Tetrahedral Si and octahedral Si monotonically increase and decrease, respectively, whereas pentahedral Si maximizes at 10–20GPa. Tetrahedral Mg decreases monotonically as P increases whereas pentahedral, octahedral and higher coordination polyhedra each show similar behavior first increasing and then decreasing after attaining a maximum; the P of the maximum for each polyhedra type migrates to higher P as the CN increases. Free oxygen and oxygen with one nearest neighbor of either Si or Mg decreases whereas Si or Mg with two or three nearest oxygens (i.e., tricluster oxygen) increases with increasing P isothermally. The increase of tricluster oxygen is consistent with spectroscopy on MgSiO3 glass quenched from 2000K and 0–40GPa and high-energy X-ray studies constraining the coordination of O around Mg and around Si at 2300K and 1bar. Coordination statistics from FPMD studies for O around Si and Si around O are in agreement with the EPMD results based on the M and OG potentials. Mg self-diffusivity is greater than O and Si self-diffusivities for both the M and OG potentials. All D values monotonically decrease with increasing pressure isothermally and all atoms are more diffusive in the M liquid compared to the OG liquid except at T >∼5000K and P >100GPa. Previously published EPMD diffusivities fall between values given by the M and OG potentials, at least up to 45GPa. The M liquid is generally less viscous than the OG liquid except at P >∼80GPa. Activation energy and volume are around 96kJ/mol and 1.5cm3/mol, respectively. The FPMD viscosity results at 120GPa and 4000 and 4500K are essentially identical to the values from the M and OG potentials. FPMD viscosity results are similar to the OG results for P <60GPa; at higher P, the FPMD viscosities are higher. At 4000K and 100GPa the shear viscosity of liquid MgSiO3 is ∼0.1Pas. More extensive laboratory results are required to better define the thermodynamic, transport and structural properties of MgSiO3 liquids and for comparison with computational studies. [Copyright &y& Elsevier]

A methodology enabling the robust treatment of model-form uncertainties in molecular dynamics simulations is proposed. The approach consists in properly randomizing a reduced-order basis, obtained by the method of snapshots in the configuration space. A multi-step strategy to identify the hyperparameters in the stochastic reduced-order basis is further introduced. The relevance of the framework is finally demonstrated by characterizing various types of modeling errors associated with molecular dynamics simulations on a graphene sheet. In particular, the ability of the framework to represent uncertainties raised by model reduction and interatomic potential selection is assessed. • Novel approach to take into account model-form uncertainties in molecular dynamics. • Approach based on the use of a stochastic reduced-order basis. • Various applications and validation on a graphene sheet. [ABSTRACT FROM AUTHOR]

The novel prophylactic agent 7-methoxytacrine-4-pyridinealdoxime is a hybrid compound formerly designed to keep acetylcholinesterase resistant to organophosphates by reactivating it in case of intoxication by such inhibitors. In rational design, a 5-carbon length-spacer hybrid compound was synthesized to evaluate its inhibitory and reactivation capabilities. In this work, theoretical results were achieved through molecular modelling techniques, taking for granted the enzymatic reactivation reaction through nucleophilic substitution. Based on the near attack conformation approach, docking studies were performed to assess the spacer-length from 1 to 10 carbons long of a series of analogues of 7-methoxytacrine-4-pyridinealdoxime. Consequently, the hybrids with length-spacer of 4 and 5 carbons long were the best assessed and subsequently subjected to further molecular dynamics simulations, complemented by Poisson-Boltzmann surface area calculations. As a result, intermolecular interactions with the different binding sites inside human acetylcholinesterase were elucidated. Besides, thermodynamics and kinetics concepts pointed to the 4-carbon linker as optimum for enzymatic reactivation. Further studies, based on quantum mechanics in conjunction with molecular mechanics, were recommended to the presented near attack conformations to achieve more thermodynamics results between the hybrids with 4- and 5-carbon linkers, like values of activation energy for the reactivation reaction. All of those in silico evaluations could be considered as a set of tools for theoretically investigate novel enzymatic reactivators with different shape of spacers. Image 1 • Nucleophile attack is relevant for the inhibited -AChE reactivation mechanism. • The near attack conformation approach (NAC) is useful for the design of reactivators. • Tyr124, Glu285, Ser298 and Glu292 are key residues to support the NAC approach. • A 4-carbon long spacer seems to be the best option for 7-MEOTA-4-PA hybrids. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • An efficient molecular modelling method for polymers is presented. • The crosslinking of an amine-cured epoxy system is modelled for three mixing ratios. • The curing process of reactive groups is characterised by near-infrared spectroscopy. • The molecular modelling process shows a good agreement with exp. NIR measurements. Abstract Reliable simulation of polymers on an atomistic length scale requires a realistic representation of the cured material. A molecular modelling method for the curing of epoxy systems is presented, which is developed with respect to efficiency while maintaining a well equilibrated system. The main criterion for bond formation is the distance between reactive groups and no specific reaction probability is prescribed. The molecular modelling is studied for three different mixing ratios with respect to the curing evolution of reactive groups and the final curing stage. For the first time, the evolution of reactive groups during the curing process predicted by the molecular modelling is validated with near-infrared spectroscopy data, showing a good agreement between simulation results and experimental measurements. With the proposed method, deeper insights into the curing mechanism of epoxy systems can be gained and it allows us to provide reliable input data for molecular dynamics simulations of material properties. [ABSTRACT FROM AUTHOR]

The paper is the first of a series of two articles on molecular models for alkanes with air components and combustion products. This article reports simulations of the vapor-liquid equilibrium phase diagram for mixtures of linear hydrocarbons with nitrogen, carbon dioxide and water. We consider four alkanes: methane, propane, octane and dodecane as characteristic components of natural gas, liquefied natural gas, gasoline and kerosene. Combustion products are presented with common computationally inexpensive molecular models: three-center models for N 2 and CO 2 , TIP4P-2005 model for water, and united-atom forcefield for alkanes. The parameters for nitrogen, CO 2 and water oxygen interactions with CH 2 and CH 3 groups are calculated with Lorentz-Berthelot mixing rules with an adjustable coefficient for the energy parameter ε , a single temperature-independent coefficient for each non-alkane component. We obtained very reasonable agreement with the experimental data for most alkane-nitrogen and alkane-carbon dioxide binary mixtures and discuss in detail the capability of the models with unified adjustable parameters. For dodecane-water system, reasonable agreement between calculated solubility of water in dodecane and experimental data was obtained; the model however is unable to represent the near-critical and high pressure phase boundaries. [ABSTRACT FROM AUTHOR]

Abstract Surface charge controls many static and dynamic properties of soft matter and micro/nanofluidic systems, but its unambiguous measurement forms a challenge. Standard characterization methods typically probe an effective surface charge, which provides limited insight into the distribution and dynamics of charge across the interface, and which cannot predict consistently all surface-charge-governed properties. New experimental approaches provide local information on both structure and transport, but models are typically required to interpret raw data. Conversely, molecular dynamics simulations have helped showing the limits of standard models and developing more accurate ones, but their reliability is limited by the empirical interaction potentials they are usually based on. This review highlights recent developments and limitations in both experimental and computational research focusing on the liquid-solid interface. Based on recent studies, we make the case that coupling of experiments and simulations is pivotal to mitigate methodological shortcomings and address open problems pertaining to charged interfaces. Graphical abstract Unlabelled Image Highlights • Standard characterization tools provide an effective, non-transferable surface charge. • Effective surface charges hide a rich structure/dynamics of charged interfaces. • New experimental methods provide local information but interpretation requires models. • Molecular dynamics provides a detailed (but approximate) atomistic description. • Coupling experiments and modeling mitigates their respective shortcomings. [ABSTRACT FROM AUTHOR]

1,2-Dichloroethane (1,2-DCE) is oxidatively converted to a carcinogenic intermediate compound, chloroacetaldehyde by chloroacetaldehyde dehydrogenase (CAldA) during its biodegradation by many bacterial strains, including Xanthobacter autotrophicus and Ancylobacter aquaticus . In this study, a 55 kDa NAD-dependent CAldA expressed by chromosomally encoded aldA gene, is reported in an indigenous Ancylobacter aquaticus UV5. A . aquaticus UV5 aldA gene was found to be 99% homologous to the plasmid (pXAU1) encoded aldA gene reported in X . autotrophicus GJ10. Pulse-field gel electrophoresis (PFGE) and PCR experiments revealed the absence of pXAU1 in A . aquaticus UV5 and that aldA was chromosomal encoded. A 6× His-tag fused CAldA cloned in pET15b, overexpressed and purified on Co-agarose affinity column using AKTA purification system showed M r of 57,526. CAldA was active optimally at pH 9 and 30 °C. The K m and v max for the substrate, acetaldehyde were found to be 115 μM and 650 mU/mg, respectively. CAldA substrate specificity was found to be low for chloroacetaldehyde, formaldehyde, propionaldehyde, butyraldehyde, benzaldehyde and glutaraldehyde as compared to acetaldehyde. Computational modeling revealed a predicted structure of CAldA consisting of five β-sheets that comprise seven antiparallel β-strands and 11 mix strands. The Molecular Dynamics and Docking studies showed that acetaldehyde bind to CaldA more tightly as compared to chloroacetaldehyde. [ABSTRACT FROM AUTHOR]

Abstract: The molecular modeling and molecular dynamics of polarization switching for the ferroelectric films model of polyvinylidene fluoride (PVDF) are investigated at the nanoscale. We consider a molecular model of PVDF film, consisting of two and four a chains [–CH2–CF2–] n limited by n=6 elementary units. The first-principle approach is applied to the switching and kinetics of these models. Two types of behavior were established for PVDF chains: simultaneous and sequential rotation in high and low electric fields. Kinetics of sequential polarization switching shows a homogeneous critical behavior in the low electric field with a critical point at Landau–Ginzburg–Devonshire (LGD) coercive field E=E C . This type of kinetics demonstrates a kink-like behavior for polarization solitary wave propagation. The simultaneous type of kinetics demonstrates the total domain-like polarization switching, corresponding to exponential behavior of switching time in high electric field as for bulk samples. Corresponding LGD intrinsic coercive field for a two-chain and four-chains model is E C ~2.0GV/m with revealing size effect. Obtained results show common quantum nature of PVDF chains switching phenomena—the quantum interaction of the PVDF molecular orbitals under applied electric field at the nanoscale level. The results obtained are compared with experimental data. [Copyright &y& Elsevier]

Based on chemical structure analysis, supplemented with fast pyrolysis results, six constitutional isomers of two-dimensional (2D) molecular models of the Huadian oil shale (HDOS) kerogen were constructed. One model yielded good agreement between simulated and experimental 13 C NMR spectra. Geometry optimization and molecular dynamics calculation were performed on three-dimensional (3D) structural models translated from the optimized 2D model. Several 3D structures were generated, including an energy-minimum 3D structure. The simulated results show that van der Waals (vdW) interactions have a greatest effect on the physical density of the HDOS kerogen. In addition, the nonbonding interactions, especially vdW interactions arisen from various flexible chains, play important role in the stabilization of the energy-minimum 3D structure. [ABSTRACT FROM AUTHOR]

Abstract: Developing the stress response using the molecular and mesoscale levels is fairly reliable during the initial strain. For instance, modulus is a property that can be established using these techniques and the continuity of scale between the molecular and mesoscale and agreement with experiment suggests that both may be used to establish modulus for parameterizing a macroscale model when measured properties are unavailable. However, the latter part of the stress–strain response that helps to establish ties to crack propagation still needs attention. One problem that was previously found in the mesoscale models was questionable lack of void formation in crosslinked systems due to superficially clean adhesive separation in the simulations. One way to overcome this lack of voiding was to determine how to develop bond breakage criterion that would allow surfaces to develop. This paper discusses development and application of bond breakage on a mesoscale level (which uses a bead-bond breakage criterion so does not explicitly define which bond is broken), and the impact on the simulated stress–strain curves using mesoscale models. [Copyright &y& Elsevier]

Abstract: Molecular integral equation theory is inverted with respect to the calculation of effective potentials for a coarse-grained, reduced molecular model composed of fewer sites than the reference. The methodology is applied to an aqueous solution of cyclohexanol as a model case, the quality of the effective potentials is studied by extensive molecular dynamics simulations. Practical guidelines for the choice of reduced model sites are worked out and perspectives for mesoscale modelling are discussed. [Copyright &y& Elsevier]

Abstract: NVT ensemble molecular dynamics simulation was performed to calculate the tracer diffusion coefficients of naphthalene and dimethylnaphthalene isomers in supercritical carbon dioxide. Carbon dioxide was treated as a Lennard-Jones molecule (single site model) and solutes were treated as a rigid model of multi sites (united atom model) and a flexible model of all atoms (all atom model). The calculated results are compared with the experimental data and the calculated results by a single site model. The united atom model gives the best results to the experimental data among the three models. The calculated tracer diffusion coefficients by the all atom model show fairly good results without adjustable interaction parameters. [Copyright &y& Elsevier]

The results of molecular modeling of ionic surfactant self-aggregation in sodium dodecyl sulphate (SDS) aqueous solutions, both salt-free and with addition of NaCl, are reported. The modeling has been based on all-atom molecular dynamics simulations at several SDS concentrations. Formation of one or three ionic aggregates of different size has been observed in the molecular dynamics runs. The computed trajectories of molecules and ions have been used to study the effects of aggregation on local densities of water molecules and counterions, and on the diffusivities of the aggregates themselves. With finding the mean force potential, the degree of counterion binding for aggregates with different aggregation numbers has been estimated. The results have been compared with the classical square-gradient density functional computations for a single ionic micelle in polar solvent. In addition, the influence of size of the simulation box on the transport properties of SDS aggregates has been investigated. In particular, we have found how the diffisivity of an ionic aggregate with a given aggregation number depends on the total surfactant concentration. The diffusivities of aggregates with aggregation numbers 16, 32, 48, and 64 at fixed total surfactant concentration have been computed. With the help of the Stokes-Einstein relation, the viscosity of the micellar solution at different total surfactant concentrations has been calculated. Time dependencies of the number of aggregates in the simulation box and of the average aggregation number during the self-assembly of surface active ions have been studied. [ABSTRACT FROM AUTHOR]

The results of molecular dynamics simulation on highly concentrated solutions of 1-1′-spiropyrrolidiniumtetrafluoroborate (SBPBF 4 ) in acetonitrile at the temperature 298 K in NVT ensemble are presented. With this objective, a new force field for SBP + cation was developed on the basis of quantum chemical calculations. It has been established that an existence of maxima on concentration dependences of conductivity is determined by the significant growth of the ion clusterization in corresponding solutions. By using quantum theory “Atom in Molecules” analysis, the significant role of weak hydrogen bonds between fluorine atoms of the anion and hydrogen atoms of the methyl and methylene groups of the cation has been established. [ABSTRACT FROM AUTHOR]

The hydration free energy Δ G s of fullerene C 60 has been determined using the quantum mechanical polarizable continuum model, microscopic free energy perturbation molecular dynamics (FEP/MD) techniques and compilation of known experimental data. The standard model density and united atom model were employed in quantum calculations. The FEP/MD values of Δ G s ( C 60 ) were calculated from modelling solute insertion in periodic water box and solute annihilation in a water sphere that additionally employed estimation of the cavitation term. The computed hydration free energy varies by up to 80 kJ mol − 1 depending on model parameters and acquires positive values when using parameterizations for fullerene. [ABSTRACT FROM AUTHOR]

In the current work, the issue of re-parameterization of Tersoff empirical potential model was addressed for 2D nanomaterial ‘germanene’ to be applied in molecular dynamics simulation based studies. The well-known chi-square minimization procedure was used to optimize the original Tersoff potential parameters. Many properties of germanene were extracted using both original and optimized Tersoff potentials and they compared with the corresponding density functional theory data. According to the results, the optimized Tersoff potential provides a significant improvement in many structural, thermodynamic, mechanical, and thermal properties of geramanene. [ABSTRACT FROM AUTHOR]

To develop more potent JAK3 kinase inhibitors, a series of CP-690550 derivatives were investigated using combined molecular modeling techniques, such as 3D-QSAR, molecular docking and molecular dynamics (MD). The leave-one-out correlation (q 2 ) and non-cross-validated correlation coefficient (r 2 ) of the best CoMFA model are 0.715 and 0.992, respectively. The q 2 and r 2 values of the best CoMSIA model are 0.739 and 0.995, respectively. The steric, electrostatic, and hydrophobic fields played important roles in determining the inhibitory activity of CP-690550 derivatives. Some new JAK3 kinase inhibitors were designed. Some of them have better inhibitory activity than the most potent Tofacitinib (CP-690550). Molecular docking was used to identify some key amino acid residues at the active site of JAK3 protein. 10 ns MD simulations were successfully performed to confirm the detailed binding mode and validate the rationality of docking results. The calculation of the binding free energies by MMPBSA method gives a good correlation with the predicted biological activity. To our knowledge, this is the first report on MD simulations and free energy calculations for this series of compounds. The combination results of this study will be valuable for the development of potent and novel JAK3 kinase inhibitors. [ABSTRACT FROM AUTHOR]

[Display omitted] • Chemical multi-component analysis on rejuvenators of aged bitumen was performed. • Multi-component molecular models of commonly-used rejuvenators were built. • Molecular dynamics simulation was carried out on pure rejuvenators. • Thermodynamics and structural properties of rejuvenators were anticipated. The molecular dynamics (MD) simulation method is proved as an efficient tool to explore the intermolecular interaction between rejuvenators and aged bitumen, but the simple "single-molecule" model of rejuvenator would bring the inaccuracy to simulation outputs due to a huge difference with its realistic multi-component chrematistic. This study aims to in-depth analyze the chemical components of four commonly-used rejuvenators with the Gas chromatography-mass spectrometry (GC–MS) method, and propose their multi-component molecular models for the first time. Further, MD simulations are performed on the multi-component models of various rejuvenators to anticipate and compare their atomic-level properties. The GC–MS results reveal that the chemical components of petroleum-based rejuvenators are more complicated than the bio-oil (BO). The alkane, naphthenic, and aromatic molecules are the main constituents of engine-oil (EO), naphthenic-oil (NO), and aromatic-oil (AO) rejuvenators. The experimental density results validate the reliability of these multi-component molecular models of four rejuvenators. From the MD simulations outputs, there is a significant difference in the energetic indices, cohesive energy density (CED), solubility parameter δ, volumetric parameters, dynamic behaviors, structural indicators, expansion coefficient (α and β), and isobaric heat capacity (C p) between the multi-component models of four rejuvenators. However, the multi-component molecular model of aromatic-oil based on the GC–MS method is not accurate because the polycyclic aromatic molecules with heavy-weight are not detected and considered. This study detects the difference in chemical components and thermodynamics properties between four rejuvenators and proposes their more realistic multi-component molecular models for further MD simulations on the rejuvenation of aged bitumen. [ABSTRACT FROM AUTHOR]

We present classical molecular dynamics (MD) and first principles molecular dynamics (FPMD) studies to investigate the transport mechanisms of hydroxide ions through poly(arylene ether sulfone ketone)s containing quaternized ammonio-substituted fluorenyl groups (QPE) as anion exchange polymers used in applications such as alkaline fuel cells. The effect of the number of repeating units in QPE on the ion conductivity of hydroxide ions was investigated by classical MD. Calculated ion conductivities are almost the same regardless of the number of repeating units in QPE and are consistent with the experimental values. The microscopic structures of water distribution in hydrated QPE were also investigated. Analysis of radial distribution functions (RDFs) of atoms calculated by classical MD implies the possibility of two different interacting conformations of hydroxide ions and ammonium groups in hydrated QPE. Distinct peaks in the RDF of O(hydroxide ion)–N(QPE) means that diffusion of hydroxide ions in hydrated QPE is mainly governed by surface diffusion, i.e., hopping between the ammonium groups of QPE, when the vehicle transport occurs. Transport of hydroxide ions based on the Grotthuss mechanism was also investigated by FPMD. The results show that hydroxide ion transport occurs with the formation of H 3 O 2 − through the hydrogen network of the water molecules. The formed H 3 O 2 − cleaves into H 2 O and OH − , resulting in proton exchange between a water molecule and a hydroxide ion, which is similar to the proton transfer mechanism observed in proton exchange membranes. [ABSTRACT FROM AUTHOR]

A series of twenty four 2-(carbazol-3-yl)-2-oxoacetamide analogues were synthesized, characterized and evaluated for their pancreatic lipase (PL) inhibitory activity. Porcine PL was used against 4-nitrophenyl butyrate (method A) and tributyrin (methods B and C) as substrates during the PL inhibition assay. Compounds 7e , 7f and 7p exhibited potential PL inhibitory activity (IC 50 values of 6.31, 8.72 and 9.58 μM, respectively in method A; and X i50 of 21.85, 21.94 and 26.2, respectively in method B). Further, inhibition kinetics of 7e , 7f and 7p against PL, using method A, revealed their competitive nature of inhibition. A comparison of the inhibition profiles of the top three compounds in methods B and C, provided a preliminary idea of covalent bonding of the compounds with Ser 152 of PL. Molecular docking studies of the compounds 7a – x into the active site of human PL (PDB ID: 1LPB ) was in agreement with the in vitro results, and highlighted probable covalent bond formation with Ser 152 apart from hydrophobic interactions with the lid domain. Molecular dynamics simulation of 7e complexed with PL, further confirmed the role of aromatic groups in stabilising the ligand (RMSD ⩽ 4 Å). The present study led to the identification of 2-(carbazol-3-yl)-2-oxoacetamide analogues 7a – x as a new class of potential PL inhibitors. [ABSTRACT FROM AUTHOR]

Molecular mobility in branched methacrylic copolymers with various concentrations of chromophore groups is studied by dielectric spectroscopy. At temperatures from −100 °С to 220 °С and in the frequency range 10 −1 –5·10 6 Hz three relaxation processes are detected. Molecular mechanisms of local β and β 1 processes and cooperative α process occurring in the glassy and in the rubbery state, respectively, are determined on the basis of the dielectric spectroscopy; molecular modeling results are consistent with experimental data. The mobility of azochromophore groups, which define nonlinear optical properties, begins at temperature 30 °С higher than that for α process. [ABSTRACT FROM AUTHOR]

Human kallikrein 5 (KLK5) is a potential target for the treatment of skin inflammation and cancer. A new series of statine based peptidomimetic compounds were designed and synthesized through simple and efficient reactions. Some KLK5 inhibitors ( 2a – c compounds) were identified with nanomolar affinity showing K i values of 0.12-0.13 μM. Our molecular modeling studies suggest that the inhibitors binding at the KLK5 through H-bond interactions with key residues (mainly His108, Gln242, Gly243, Ser245, and Ser260), disrupting the correlated motions mainly among the Ile67-Tyr127, Glu128-Val187, and Gly237-Ser293 subdomains, which seems to be crucial for KLK5 activity. Therefore, we believe that these findings will significantly facilitate our understanding of the conformational dynamics in the course of KLK5 inhibition and, consequently, the development of more potent molecules as alternative for cancer treatment. [ABSTRACT FROM AUTHOR]

Abstract: Molecular dynamics and molecular mechanics simulations are used to establish well-equilibrated, validated molecular models of the EPON 862-DETDA epoxy system with a range of crosslink densities using a united atom force field. Molecular dynamics simulations are subsequently used to predict the glass transition temperature, thermal expansion coefficients, and elastic properties of each of the crosslinked systems. The results indicate that glass transition temperature and elastic properties increase with increasing levels of crosslink density and the thermal expansion coefficient decreases with crosslink density, both above and below the glass transition temperature. The results demonstrate reasonable agreement with thermomechanical properties in the literature. The results also indicate that there may be a range of crosslink densities in epoxy systems beyond which there are limited changes in thermomechanical properties. [Copyright &y& Elsevier]

Abstract: Taking correctly into account long ranged interactions in molecular simulations of molecular models based on classical atomistic representations are essential to obtain reliable results on model systems and in simulations of biological systems. A lot of numerical methods have been developed to this end; the most important of them are reviewed in this paper. Particular attention is paid to the analytical relations between the methods, this allows comparisons on efficiency and accuracy between them and also to proceed to precise implementations of these techniques. While most of the methods have been developed for Coulomb interactions, we give also some analytical details to apply these methods to screened Coulomb (Yukawa interactions), inverse power law and dipolar interactions. Particular types of systems, the quasi-2D systems, are also considered in this paper. Quasi-2D systems represent a large class of physical systems where the spatial extension in one direction of the space is very small by comparison to the other two. These representations are very useful to describe the properties of interfaces, surfaces, fluids confined in slab geometry, etc. In computer simulations, these systems are studied with partial periodic boundary conditions: periodic boundary conditions are taken in directions where spatial extensions are large and some other boundary conditions are taken in directions with smaller extensions. In this review, we describe also the numerical methods developed to handle long ranged interactions in numerical simulations of quasi-2D systems. The properties of quasi-2D systems depend strongly on interactions between components; more specifically electrostatic and magnetic interactions and interactions with external fields are of particular interest in these systems. [Copyright &y& Elsevier]

Hydrochloride salt formation for Active Pharmaceutical Ingredients (APIs) is the primary choice to impart aqueous solubility and to promote dissolution. Dipyridamole (DIP) is a cardiovascular drug which is practically insoluble in water. We discovered a new form of DIP called as dipyridamole hydrochloride trihydrate (DIPHT), which was prepared by an unusual method of reacting the DIP with hydrated hydrochloric acid (HCl) that was liberated in situ by the reaction of ferric chloride with water. The liberated HCl was consumed as reagent in situ by the scavenger (API) and was converted to a hydrochloride trihydrate. The product was characterized by FTIR, mass spectroscopy, PXRD and DSC. Supramolecular structure of this novel DIPHT was revealed by single crystal XRD. A sustained intramolecular hydrogen bond alliance was found in DIP and the DIPHT. Stability of this hydrogen bond was further evaluated by means of molecular modelling studies. We performed electron calculations using quantum mechanics (QM) on both the base and salt structures to compare their geometry and molecular orbital energy levels. Molecular Dynamics (MD) simulations were also conducted in explicit solvent models to provide more insights into the hydrogen bond strength and conformational preferences of the base and salt structure. Together with QM and MD, we were able to explain the influence of hydrogen bonds on proton uptake activity of DIP and stability of DIP and DIPHT. DIPHT which can dissolve faster than DIP in water may enhance the dissolution and bioavailability of the drug. As the current drug development research is shifting to repurpose the existing drugs in order to subside the untoward risks in new drug development, we believe that DIPHT with its intrinsic aqueous solubility could bring more application for DIP and generate interest within the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Although corrosion inhibitors are largely used to prevent chloride-induced corrosion in reinforced concrete structures, their interaction mechanisms with the passive film present on steel still requires deeper understanding. This work combines experimental techniques with theoretical calculations, based on molecular mechanics and molecular dynamics methods of the adsorbed inhibitors on γ-FeOOH, to provide insight into the interactions between five organic inhibitors and carbon steel in a chloride-rich alkaline environment. A strong physisorption of inhibitors on the substrate was observed, while the distribution of specific groups – carboxylate anions or amino groups – and interactions among inhibitor molecules determined through molecular simulations drive the corrosion inhibition efficiency of the adsorbed layer. [ABSTRACT FROM AUTHOR]

Coagulation factor Xa (Factor Xa, FXa) is a particularly promising target for novel anticoagulant therapy. The first oral factor Xa inhibitor has been approved in the EU and Canada in 2008. In this work, 38 [6,6,5] Tricyclic Fused Oxazolidinones were studied using a combination of molecular modeling techniques including three-dimensional quantitative structure–activity relationship (3D-QSAR), molecular docking, molecular dynamics and Topomer CoMFA (comparative molecular field analysis) were used to build 3D-QSAR models. The results show that the best CoMFA model has q 2 = 0.511 and r 2 = 0.984, the best CoMSIA (comparative molecular similarity indices analysis) model has q 2 = 0.700 and r 2 = 0.993 and the Topomer CoMFA analysis has q 2 = 0.377 and r 2 = 0.886. The results indicated the steric, hydrophobic, H-acceptor and electrostatic fields play key roles in models. Molecular docking and molecular dynamics explored the binding relationship of the ligand and the receptor protein. [ABSTRACT FROM AUTHOR]

The radioactive decay of 40 K to 40 Ar is the basis of isotope age determination of micaceous clay minerals formed during diagenesis. The difference in K–Ar ages between fine and coarse grained illite particles has been interpreted using detrital-authigenic components system, its crystallization history or post-crystallization diffusion. Yet another mechanism should also be considered: natural 40 Ar recoil. Whether this recoil mechanism can result in a significant enough loss of 40 Ar to provide observable decrease of K–Ar age of the finest illite crystallites at diagenetic temperatures – is the primary objective of this study which is based on molecular dynamics (MD) computer simulations. All the simulations were performed for the same kinetic energy (initial velocity) of the 40 Ar atom, but for varying recoil angles that cover the entire range of their possible values. The results show that 40 Ar recoil can lead to various deformations of the illite structure, often accompanied by the displacement of OH groups or breaking of the Si–O bonds. Depending on the recoil angle, there are four possible final positions of the 40 Ar atom with respect to the 2:1 layer at the end of the simulation: it can remain in the interlayer space or end up in the closest tetrahedral, octahedral or the opposite tetrahedral sheet. No simulation angles were found for which the 40 Ar atom after recoil passes completely through the 2:1 layer. The energy barrier for 40 Ar passing through the hexagonal cavity from the tetrahedral sheet into the interlayer was calculated to be 17 kcal/mol. This reaction is strongly exothermic, therefore there is almost no possibility for 40 Ar to remain in the tetrahedral sheet of the 2:1 layer over geological time periods. It will either leave the crystal, if close enough to the edge, or return to the interlayer space. On the other hand, if 40 Ar ends up in the octahedral sheet after recoil, a substantially higher energy barrier of 55 kcal/mol prevents it from leaving the TOT layer over geological time. Based on the results of MD simulations, the estimates of the potential effect of 40 Ar recoil on the K–Ar dating of illite show that some of 40 Ar is lost and the loss is substantially dependent on the crystallite dimensions. The 40 Ar loss can vary from 10% for the finest crystallites (two 2:1 layers thickness and <0.02 μm in diameter) to close to zero for the thickest and largest (in the ab plane) ones. Because the decrease of the K–Ar estimated age is approximately proportional to the 40 Ar loss, the finer crystallites show lower apparent age than the coarser ones, although the age of crystallization is assumed equal for all the crystallites. From the model it is also clear that the lack of K removal from illite fringes (potentially Ar-free) strongly increases the apparent age differences among crystallites of different size. [ABSTRACT FROM AUTHOR]

The glucose phosphorylating enzyme glucokinase (GK) is a 50 kD monomeric protein having 465 amino acids. It maintains glucose homeostasis inside cells, acts as a glucose sensor in pancreatic β-cells and as a rate controlling enzyme for hepatic glucose clearance and glycogen synthesis. It has two binding sites, one for binding d -glucose and the other for a putative allosteric activator named glucokinase activator (GKA). The GKAs interact with the same region of the GK enzyme that is commonly affected by naturally occurring mutations in humans. However, many GKAs do not bind to GK in the absence of glucose. Recently, it has been reported that GKAs are highly effective in patients with type 2 diabetes mellitus. In this milieu a molecular modeling study has been carried out on three natural variants of GK that lie in the GKA binding site and are known to cause maturity onset diabetes of young (MODY). Additionally, a 10 ns molecular dynamics simulation was done on each of the modeled variant in order to explore the flexibility of this site. Subsequently, a systematic virtual screening study was done to identify compounds which can bind with high affinity at GKA binding site of mutant GK. [ABSTRACT FROM AUTHOR]

Psychiatric disorders, such as schizophrenia, bipolar disorder and major depression, are paid more and more attention by human due to their upward tendency in modern society. D 2 -like and 5-HT 2A receptors have been proposed as targets of antipsychotic drugs. Atypical antipsychotic drugs have been deemed to improve the treatment of positive, negative and extrapyramidal symptoms. Unfortunately, no experimental structures for these receptors are available except D 3 receptor (D 3 R). Therefore, it is necessary to construct structures of D 2 -like and 5-HT 2A receptors to investigate the interaction between these receptors and their antagonists. Accordingly, homology models of dopamine D 2 , D 3 , D 4 and serotonin 5-HT 2A receptors have been built on the high-resolution crystal structure of the β 2 -adrenergic receptor, and refined by molecular dynamics simulations. The backbone root-mean-square deviation (RMSD) of D 3 R model relative to crystal structure is 1.3 Å, which proves the reliability of homology modeling. Docking studies reveal that the binding modes of four homology models and their antagonists are consistent with experimental site-directed mutagenesis data. The calculated p K i values agree well with the experimental p K i ones. Antagonists with linear structures such as butyrophenones and benzisoxazolyl piperidines are easily docked into D 2 -like and 5-HT 2A receptors. Polycyclic aromatic compounds have weaker affinity with four receptors. Homology models of D 2 -like and 5-HT 2A receptors will be helpful for predicting the affinity of novel ligands, and could be used as three-dimensional (3D) templates for antipsychotic virtual screening and further drug discovery. [ABSTRACT FROM AUTHOR]

Raney Nickel is a nanostructured catalyst which is used in a variety of industrial processes. It has a characteristic porous, amorphous structure. Since the structure of both the precursor alloy and the active form of Raney Nickel is determining the catalytic activity and performance, it is crucial to use realistic porous structures for simulating the catalytic reaction. The simulation protocol for the formation of porous Raney Nickel is shown in this study. The structures are then characterized in silico by means of typical characteristics such as the pore size, pore size distribution, density, free volume and free surface. In addition to this, the influence of the Aluminum content in the final form of the catalyst after pore formation is investigated. Furthermore, the cell size of the unit cell was doubled in x , y , and z directions to elucidate the influence of the impact of the cell size on the pore size. [ABSTRACT FROM AUTHOR]

Although there are many successful descriptions of the mechanical response of dermis at different levels of complexity and incorporating varying degrees of the physical phenomena involved in deformation, observations indicate that the unraveling of fibers involves a complex three-dimensional process in which they interact in ways that resemble a braided pattern. Here we develop two complementary treatments to gain a better understanding of the mechanical response of dermis: a) an analytical treatment incorporating fibril stiffness, interfibrillar frictional sliding, and the effect of lateral fibers on the extension of a primary fiber; b) a coarse-grained molecular dynamics model comprised of an array of parallel curved fibrils simulating a fiber. Interfibrillar frictional sliding and stiffness are also captured. Both analytical and molecular dynamics models operate at a scale compatible with the wavelength of collagen fibers (~10 µm). The constitutive description presented here incorporates important physical processes taking place during deformation of dermis and thus represents an advance in our understanding of these phenomena. Microstructural observations of the dermis of skin during tensile deformation indicate that the unraveling of fibers involves a complex three-dimensional process which replicates the effects of braiding. Two complementary constitutive modeling treatments were developed to gain a better understanding of the mechanical response of dermis: an analytical treatment incorporating fibril stiffness, interfibrillar sliding, and the effect of transverse fibers; and a coarse-grained molecular dynamics model describing the fibril bundling effect. An important novel aspect of the current contribution is the recognition that tridimensional collagen fiber arrangements play an important role in the mechanical response. The constitutive description presented here incorporates physical processes taking place during deformation of the dermis and thus represents an advance in our understanding of these phenomena. Image, graphical abstract [ABSTRACT FROM AUTHOR]

In the present work, we applied docking and molecular dynamics techniques to study 11 compounds inside the enzymes dihydrofolate reductase (DHFR) from the biological warfare agent Bacillus anthracis ( Ba DHFR) and Homo sapiens sapiens ( Hss DHFR). Six of these compounds were selected for a study with the mutant Ba F96IDHFR. Our results corroborated with experimental data and allowed the proposition of a new molecule with potential activity and better selectivity for Ba DHFR. [ABSTRACT FROM AUTHOR]

The atomistic model of amorphous silicon-carbide membrane that was developed in Parts I and II of this series is utilized in nonequilibrium molecular dynamics (MD) simulations to study transport and separation of equimolar gaseous mixtures H 2 /CO 2 and H 2 /CH 4 in the membrane at high temperatures. We simulated membranes with up to about 39 nm in thickness, containing up to 170,000 atoms, and up to 100 ns to obtain reliable statistics. The effect of parameters such as the temperature, the applied pressure drop across the system, and the membrane׳s thickness on the separation properties was studied. The trends in the dependence of the separation factor on the membrane׳s thickness are consistent with experiments, namely the separation factor increases with the thickness up to an optimal value, beyond which it remains constant, or may even decrease. The dependence of the computed separation factor on the membrane׳s thickness is used in conjunction with the experimental values of the separation factor to estimate the thickness of actual membranes. The results are in agreement with the experimental data, demonstrating the value of MD simulations with a reactive force field for characterizing the properties of complex amorphous films, and flow and transport therein. [ABSTRACT FROM AUTHOR]

Human α- l -iduronidase (IDUA) is a member of glycoside hydrolase family and is involved in the catabolism of glycosaminoglycans (GAGs), heparan sulfate (HS) and dermatan sulfate (DS). Mutations in this enzyme are responsible for mucopolysaccharidosis I (MPS I), an inherited lysosomal storage disorder. Despite great interest in determining and studying this enzyme structure, the lack of a high identity to templates and other technical issues have challenged both bioinformaticians and crystallographers, until the recent publication of an IDUA crystal structure (PDB: 4JXP ). In the present work, four alternative IDUA models, generated and evaluated prior to crystallographic determination, were compared to the 4JXP structure. A combined analysis using several viability assessment tools and molecular dynamics simulations highlights the strengths and limitations of different comparative modeling protocols, all of which are based on the same low identity template (only 22%). Incorrect alignment between the target and template was confirmed to be a major bottleneck in homology modeling, regardless of the modeling software used. Moreover, secondary structure analysis during a 50 ns simulation seems to be useful for indicating alignment errors and structural instabilities. The best model was achieved through the combined use of Phyre 2 and Modeller, suggesting the use of this protocol for the modeling of other proteins that still lack high identity templates. [ABSTRACT FROM AUTHOR]

3-Hydroxy-3-methylglutaryl coenzyme-A reductase (HMGR) is generally regarded as targets for the treatment of hypercholesterolemia. HMGR inhibitors (more commonly known as statins) are discovered as plasma cholesterol lowering molecules. In this work, 120 atorvastatin analogues were studied using a combination of molecular modeling techniques including three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking and molecular dynamics (MD) simulation. The results show that the best CoMFA (comparative molecular field analysis) model has q2=0.558 and r2=0.977, and the best CoMSIA (comparative molecular similarity indices analysis) model has q2=0.582 and r2=0.919. Molecular docking and MD simulation explored the binding relationship of the ligand and the receptor protein. The calculation results indicated that the hydrophobic and electrostatic fields play key roles in QSAR model. After MD simulation, we found four vital residues (Lys735, Arg590, Asp690 and Asn686) and three hydrophobic regions in HMGR binding site. The calculation results show that atorvastatin analogues obtained by introduction of F atoms or gem-difluoro groups could obviously improve the inhibitory activity. The new HMGR inhibitor analogues design in this Letter had been submitted which is being currently synthesized by our laboratories. [ABSTRACT FROM AUTHOR]

Highlights: [•] Homology model of human protein arginine methyltransferase 1 was built. [•] MD simulation and ASP were used to consider receptor flexibility. [•] Cavity around ASP84 was proposed as a potential binding site. [•] The predominant binding poses of known ligands were proposed. [ABSTRACT FROM AUTHOR]

Abstract: Fluoride salts and their interactions with metals are of wide interest for the nuclear community. In this work, first-principles molecular dynamics (FPMD) was employed to study both pure molten fluoride salt and fluoride salt with dissolved solute Cr ions (a common corrosion product) at high temperature (823–1423K). Two types of molten fluoride salts, namely flibe (LiF–BeF2) and flinak (LiF–NaF–KF), with the Cr0, Cr2+ and Cr3+ ions were chosen as a target system for the FPMD modeling. The prediction of thermo-kinetic properties of pure fluoride salt, such as the equilibrium volume, density, bulk modulus, coefficient of thermal expansion, and self-diffusion coefficient, provide useful extensions of existing data and verify the accuracy of the FPMD simulation in modeling of fluoride salts. The FPMD modeling of solute Cr in fluoride salt shows the effect of Cr valence on diffusivity and local structure in the salt. [Copyright &y& Elsevier]

Abstract: The ever-increasing gap between the availabilities of the genome sequences and the crystal structures of proteins remains one of the significant challenges to the modern drug discovery efforts. The knowledge of structure-dynamics-functionalities of proteins is important in order to understand several key aspects of structure-based drug discovery, such as drug–protein interactions, drug binding and unbinding mechanisms and protein–protein interactions. This review presents a brief overview on the different state of the art computational approaches that are applied for protein structure modelling and molecular dynamics simulations of biological systems. We give an essence of how different enhanced sampling molecular dynamics approaches, together with regular molecular dynamics methods, assist in steering the structure based drug discovery processes. [Copyright &y& Elsevier]