All-atom Force Field Research Articles

Research on the viscosity characteristics of water glycol hydraulic fluids in deep-sea environment from molecular dynamics

The utilization of water glycol as a working medium represents a significant advancement in the realm of deep-sea hydraulic transmission systems. The viscosity of water glycol is a crucial parameter for hydrodynamic lubrication, yet it is profoundly influenced by the environmental conditions of the deep sea. This study employs the TIP4P/2005 water molecule model in conjunction with the optimized potentials for liquid simulations all-atom force field, and non-equilibrium molecular dynamics method to predict the viscosity of water glycol hydraulic fluids with varying compositions under deep-sea conditions. The simulation values agree well with the experimental results. Furthermore, this study introduces a fitting equation that accounts for the effects of composition, temperature, and pressure, enabling the prediction of the viscosity of water glycol hydraulic fluids within the 0–11 000 m sea water environment.

Force field comparison for molecular dynamics simulations of liquid membranes

To accelerate the development of liquid ion-selective barriers based on ethers, we compare the all-atom force fields GAFF, OPLS-AA with charge correction 1.14*CM1A (OPLS-AA/CM1A), CHARMM version 36 (CHARMM36), and COMPASS for diisopropyl ether (DIPE) to determine the most appropriate model for further simulations of liquid membranes. Utilizing the selected force fields, we calculate the density and shear viscosity of DIPE across a temperature range of 243–333 K. Furthermore, we use CHARMM36 with mTIP3P water model and COMPASS with its own water model to evaluate the mutual solubility and interfacial tension between DIPE and water, estimate the partition coefficients of ethanol in DIPE + Ethanol + Water systems. Based on our comparative study, we conclude that CHARMM36 is the most suitable force field for modeling ether-based liquid membranes.

Effect of hydrogen constraints on predicting thermal conductivity of hydrocarbons in molecular dynamics simulation

Large overestimation has been reported while predicting the thermal conductivity of hydrocarbons using an all-atom force field model in molecular dynamics (MD) simulations. Although it has been guessed as resulting from the high-frequency vibration of the hydrogen atoms and hydrogen constraints method is suggested to be employed to reduce the deviation, how hydrogen constraints affect the heat conduction and local structure of hydrocarbons in MD simulation is still not fully understood. In this work, the effect of hydrogen constraints on the prediction of thermal conductivity of n-decane in MD simulations with the all-atom force field is studied. The results show that the deviation of the thermal conductivity of n-decane can be narrowed down by 72.48 % in simulations if the hydrogen constraints with a SHAKE algorithm is employed. The analysis of heat flux decomposition indicates that employing hydrogen constraints can reduce the contribution of transport term and non-bonded interactions to the heat flux, which in turn can help improve the accuracy while predicting the thermal conductivity in MD simulations. Furthermore, results of the vibrational density of states show that hydrogen constraints can dismiss the high-frequency vibration mode of molecules, thus effectively reducing the overestimation of thermal conductivity of hydrocarbon systems in MD simulations. The findings of this work sheds light on the molecular mechanism of heat transfer in hydrocarbon systems.

Effect of Protein-Polarized Ligand Charges on Relative Protein Ligand Binding Affinities.

A major challenge in computer-aided drug design is predicting relative binding energies of different molecules to a target protein using fast and accurate free-energy calculation methods. Free-energy calculations are primarily computed by utilizing classical molecular dynamics simulations based on all-atom force fields (FF) to model the interactions in the system. The present standard classical all-atom FFs contain fixed partial charges on the atoms, and hence electrostatic interactions are modeled between them. The parametrization process to determine these partial charges usually relies on quantum mechanics or semiempirical calculations of the molecule in the gas phase or homogeneous water surrounding. These present standard parametrization schemes of the partial charges neglect, therefore, polarization effects from the protein surrounding. The absence of protein polarization effects can lead to significant errors in free-energy calculations in proteins. We present a parametrization scheme for the partial charges of ligands, named protein-induced polarization (PIP) charges, which account for the electrostatic polarization due to the protein surrounding. The scheme involves single-point quantum mechanics/molecular mechanics calculations of the ligand charges in the protein/water surrounding. Using PIP ligand partial charges, we have calculated the relative binding free energies (RBFEs) of well-studied protein-ligand systems. We show here that RBFEs computed with PIP charges are either significantly improved or at least comparable to those computed with nonpolarized standard GAFF charges. Overall, we present a simple-to-use parametrization scheme to include protein polarization in any type of binding free-energy calculations. The parametrization scheme increases the accuracy in RBFE calculations, while it does not add significant computation time to standard parametrization procedures.

Self diffusion, viscosity, and surface tension estimations of amines by using AUA4 force field

Accurate and efficient molecular dynamic simulation of amine functional group is crucial for designing improved carbon dioxide absorption processes, as thermodynamic and transport properties can be concurrently calculated with molecular-level insight. The exploration of these properties has been limited, and all-atom force fields have struggled to cope with the dynamic and equilibrium characteristics of amines, especially monoethanolamine, which possess and exceptionally low self-diffusivity. In response to this situation, we propose using an anisotropic united atom (AUA4) force field, which strikes a balance between precision and performance allowing to predict the key transport and equilibrium properties involved in mass transfer units. A total of 7 amines were included in this study. Among the main results observed in this work, there was excellent recreation of density. The surface tension evidenced performance similar to other transferable force fields with a general positive deviation of 20%. Regarding transport properties, methylamine and linear alkylamines shows moderate uniform deviations. Trimethylamne, being the only one tertiary amine, exhibited higher deviations than the other amines. In contrast, excellent results were obtained for ET-DI, while significant deviations were found for MEA. Nevertheless, in light of previous studies on this alkanolamine, these deviations appear promising. Finally, we were able to achieve the best predictions of the currently available force fields for ethanolamine by increasing its torsional barriers. This allowed us to accurately reproduce its low self-diffusion and viscosity while maintaining its main structural features.

Determining interfacial tension and critical micelle concentrations of surfactants from atomistic molecular simulations

HypothesisAtomistically-detailed models of surfactants provide quantitative information on the molecular interactions and spatial distributions at fluid interfaces. Hence, it should be possible to extract from this information, macroscopical thermophysical properties such as interfacial tension, critical micelle concentrations and the relationship between these properties and the bulk fluid surfactant concentrations.Simulations and ExperimentsMolecular-scale interfacial of systems containing n-dodecyl β-glucoside (APG12) are simulated using classical molecular dynamics. The bulk phases and the corresponding interfacial regions are all explicitly detailed using an all-atom force field (PCFF+). During the simulation, the behaviour of the interface is analyzed geometrically to obtain an approximated value of the critical micelle concentration (CMC) in terms of the surfactant area number density and the interfacial tension is assessed through the analysis of the forces amongst molecules.New experimental determinations are reported for the surface tension of APG12 at the water/air and at the water/n-decane interfaces.FindingsWe showcase the application of a thermodynamic framework that inter-relates interfacial tensions, surface densities, CMCs and bulk surfactant concentrations, which allows the in silico quantitative prediction of interfacial tension isotherms.

A comparative study on the solubility of CH3SH and H2S in imidazolium-based ionic liquids: A connectionist approach between free volume and thermodynamics

Sulfur contaminants in industrial gas streams, such as hydrogen sulfide and mercaptans, must be eliminated due to safety and environmental considerations. Ionic liquids, as a new class of chemical compounds, are an alternative to conventional aqueous alkanolamine solutions currently used in absorption gas treatment processes. In this work, the solubilities of methyl mercaptan (CH3SH) and hydrogen sulfide gases in 1-butyl-3-methylimidazolium-based ionic liquids with tetrafluoroborate ([C4mim][BF4]), hexafluorophosphate ([C4mim][PF6]), trifluoromethanesulfonate ([C4mim][OTf]), and bis(trifluoromethylsulfonyl)imide ([C4mim][Tf2N]) anions have been studied using molecular dynamics (MD) simulation and a recently developed OPLS all-atom (OPLS-AA-0.8) force field. A new concept, the induced free volume, has been introduced in this work, which provides a realistic and precise connection between the thermodynamic entropic contributions to the dissolution process of CH3SH and H2S in the ionic liquids, on one hand, and the microscopic free/void volume induced as a result of the entrance of a gas solute molecule into the liquid structure, on the other hand. The thermodynamic energetic contributions were correlated to the CH3SH/H2S interaction with the ionic species of the ionic liquids. Quantum chemical energy decomposition analysis (EDA) was employed to calculate and analyze the binding interaction and nature of CH3SH/H2S interactions with the ionic species of ionic liquids. It was found that the van der Waals contributions to the interaction of CH3SH with ionic liquids are more significant compared to that of H2S, while the opposite conclusion could be deduced for the corresponding electrostatic contributions. Both CH3SH and H2S established equivalent hydrogen bonding interactions with the ionic liquids studied in this work. The diffusion coefficients of the ionic species, as well as the excess chemical potentials and Henry’s constants for the dissolution of CH3SH and H2S in the ionic liquids, were calculated by free energy perturbation technique (FEP) and compared with the MD simulated and experimental data, reported in the literature. It was concluded that the OPLS-AA-0.8 force field yields Henry’s constants and diffusivities that are in better agreement with the reliable experimental data corresponding to other OPLS versions reported to date.

Elasticity of bilayer lipid membranes from their density correlation function

ABSTRACT We study the density correlation function (DCF) of DPPC lipid bilayers. We compare Molecular Dynamics (MD) results with theoretical predictions obtained with a mesoscopic description, in terms of the lipid membrane elasticity. One key objective of our work is the quantification of the lipid membrane elasticity directly from the DCF, both for the membrane undulations and local membrane thickness. Our method does not require the definition of instantaneous surfaces or internal variables defining lipid orientations. Building on our previous work, here we focus on the intralayer correlations, i.e. the DCF of lipids residing on the same monolayer, by tracking only the position of the phosphorus atoms in a lipid head group. We demonstrate the relevance of the intralayer two-dimensional (2D) correlations to the total DCF. We further show that all-atom (AA) and coarse grained (CG) lipid forcefields, feature distintively different DCFs. The CG forcefield predicts results in good agreement with the mesoscopic predictions, for the entire wavevector range; the AA forcefield (CHARMM36) predict strong peristaltic fluctuations at long wavevectors q ≳ 0.8 nm − 1 , which are absent in the CG lipid model (MARTINI).

Critical assessment of popular biomolecular force fields for molecular dynamics simulations of folding and enzymatic activity of main protease of coronavirus SARS-CoV-2

The main cysteine protease (Mpro) of coronavirus SARS-CoV-2 has become a promising target for computational development in anti-COVID-19 treatments. Here, we benchmarked the performance of six biomolecular molecular dynamics (MD) force fields (OPLS-AA, CHARMM27, CHARMM36, AMBER03, AMBER14SB and GROMOS G54A7) and three water models (TIP3P, TIP4P and SPC) for reproducing the native fold and the enzymatic activity of Mpro as monomeric and dimeric units. The MD sampling up to 1 μs suggested that the proper choice of the force fields and water models plays an essential role in reproducing the tertiary structure and the inter-residue distance between the catalytic dyad His41-Cys145. We found that while most benchmarked all-atom force fields reproduce well the native fold of Mpro, the CHARMM27/TIP3P and OPLS-AA/TIP4P setups revealed a good performance in reproducing the structure of the catalytic domain. In addition, these FF setups were also well-adopted for MD sampling of Mpro at the physiologic conditions by mimicking the presence of 100 mM NaCl and the elevated temperature of 310 K. Finally, both FFs were also performed well in reproducing the native fold of Mpro in a dimeric form. Therefore, comparing the preservation of the native fold of Mpro and the stability of its catalytic site architecture, our MD benchmarking suggests that the OPLS-AA/TIP4P and CHARMM27/TIP3P MD setups at the physiologic conditions may be well-suited for rapid in silico screening and developing broad-spectrum anti-coronaviral therapeutic agents.

A force field for the solubility of cellulose in DMSO/Ionic liquids

AbstractWe present the extension of our all-atom force field BILFF (Bio-polymers in Ionic Liquids Force Field) to the co-solvent dimethyl sulfoxide (DMSO). BILFF already includes force field parameters for several imidazolium- and triazolium-based ionic liquids, water, and the bio-molecule cellulose. DMSO is known to increase the cellulose solubility of [EMIm][OAc] when applied as an additive. Our focus is on a correct reproduction of the hydrogen bonds in the ternary system of [EMIm]$$^+$$ + , [OAc]$$^-$$ - , water and DMSO compared to ab initio molecular dynamics simulations. For this purpose, the results from force field MD simulations such as radial and distance–angle distribution functions are compared with the reference AIMD simulation. Based on this, the force field parameters (starting from OPLS–AA) are iteratively adjusted. Four systems, pure and aqueous DMSO as well as DMSO in pure and aqueous [EMIm][OAc], are considered and additionally compared to DMSO-free [EMIm][OAc] systems. A very good agreement with respect to the microstructure of the quantum chemical reference simulations as well as to experimental data such as density, diffusion coefficients, enthalpy of vaporization, compressibility and thermal expansion coefficients can be observed over a wide temperature range. BILFF thus enables accurate simulations of larger systems of solvated cellulose in (aqueous) [EMIm][OAc] and the co-solvent DMSO.

Photoresponsive Azobenzene Nanocluster-Modified Liposomes: Mechanism Analysis Combining Experiments and Simulations.

Stimuli-responsive behaviors and controlled release in liposomes are pivotal in nanomedicine. To this end, we present an approach using a photoresponsive azobenzene nanocluster (AzDmpNC), prepared from azobenzene compounds through melting and aggregation. When integrated with liposomes, they form photoresponsive vesicles. The morphology and association with liposomes were investigated by using transmission electron microscopy. Liposomes loaded with calcein exhibited a 9.58% increased release after UV exposure. To gain insights into the underlying processes and elucidate the mechanisms involved. The molecular dynamic simulations based on the reactive force field and all-atom force field were employed to analyze the aggregation of isomers into nanoclusters and their impacts on phospholipid membranes, respectively. The results indicate that the nanoclusters primarily aggregate through π-π and T-stacking forces. The force density inside the cis-isomer of AzDmpNC formed after photoisomerization is lower, leading to its easier dispersion, rapid diffusion, and penetration into the membrane, disrupting the densification.

Advancing Sustainable Solutions: Exploring United Atom Model for Efficient Molecular Dynamics Simulation of Poly-ethylene Vanillic (PEV) Polymer

The development of green polymers is a crucial long-term solution to address the problem of plastic waste. In particular, the bio-based polymer polyethylene vanillic (PEV) has garnered interest due to its comparable mechanical and thermal properties to polyethylene terephthalate (PET), a widely used single-use plastic. Molecular dynamics (MD) simulations are commonly employed to study the molecular structure and dynamic properties of materials, offering cost-effective applications. However, the accuracy of MD simulation results heavily relies on the chosen force field model. The all-atom (AA) force field, while providing insights into molecular interactions, demands significant computational resources, especially for large systems like polymers. This study aimed to employ the united atom (UA) model with revised OPLS-UA force field parameters for the biopolymer PEV, aiming to reduce computational time in dynamic and physical investigations. Consequently, the UA model successfully folded the PEV polymer in a manner resembling the single-chain PEV treated with the AA model, while also predicting a glass transition temperature (Tg) close to the experimental value of 348 K. These findings underscore the potential of the UA model for simulating PEV and its promising implications.

Scaling towards the critical point in the combined reaction/Gibbs ensemble

We explore the impact of force field parameters and reaction equilibrium on the scaling behavior towards the critical point in reactive binary systems, focusing on NO2/N2O4. This system can be considered as a special single-component system since NO2 and N2O4 are in chemical equilibrium via the chemical reaction 2NO2⇌N2O4. We simplify the system by representing both components as single LJ particles, achieving excellent agreement with densities computed using molecular simulations in which all-atom force fields were used. We investigate the effect of force field parameters (ɛ and σ) on phase behavior and show that the critical exponent β remains constant, which means that intermolecular interactions do not affect the scaling to the critical point when the chemical reaction takes place. We also investigate the sensitivity of the reaction equilibrium constant and show that even small changes in isolated molecule partition functions lead to large differences in chemical equilibria. We show that the critical exponent β is different for systems with different reaction equilibrium constants, so a careful parameterization of β is needed for an accurate computation of critical temperatures of reactive mixtures. We perform a screening of reactive binary mixtures for a wide range of ideal gas reaction equilibrium constants, revealing key insights into the thermodynamic behavior and critical properties. Thereby we facilitate the efficient screening of reactive binary mixtures for various applications. Our results emphasize the importance of accurately parameterizing β and provide valuable insights into the critical scaling behavior of complex reactive systems.

Rationally Designed Novel Antimicrobial Peptides Targeting Chitin Synthase for Combating Soybean Phytophthora Blight.

Soybean phytophthora blight is a severe menace to global agriculture, causing annual losses surpassing USD 1 billion. Present crop loss mitigation strategies primarily rely on chemical pesticides and disease-resistant breeding, frequently surpassed by the pathogens' quick adaptive evolution. In this urgent scenario, our research delves into innovative antimicrobial peptides characterized by low drug resistance and environmental friendliness. Inhibiting chitin synthase gene activity in Phytophthora sojae impairs vital functions such as growth and sporulation, presenting an effective method to reduce its pathogenic impact. In our study, we screened 16 previously tested peptides to evaluate their antimicrobial effects against Phytophthora using structure-guided drug design, which involves molecular docking, saturation mutagenesis, molecular dynamics, and toxicity prediction. The in silico analysis identified AMP_04 with potential inhibitory activity against Phytophthora sojae's chitin synthase. Through three rounds of saturation mutagenesis, we pin-pointed the most effective triple mutant, TP (D10K, G11I, S14L). Molecular dynamic simulations revealed TP's stability in the chitin synthase-TP complex and its transmembrane mechanism, employing an all-atom force field. Our findings demonstrate the efficacy of TP in occupying the substrate-binding pocket and translocation catalytic channel. Effective inhibition of the chitin synthase enzyme can be achieved. Specifically, the triple mutant demonstrates enhanced antimicrobial potency and decreased toxicity relative to the wild-type AMP_04, utilizing a mechanism akin to the barrel-stave model during membrane translocation. Collectively, our study provides a new strategy that could be used as a potent antimicrobial agent in combatting soybean blight, contributing to sustainable agricultural practices.

An All-Atom Force Field for Dry and Water-Lubricated Carbon Tribological Interfaces

An All-Atom Force Field for Dry and Water-Lubricated Carbon Tribological Interfaces

Free-energy landscapes of transmembrane homodimers by bias-exchange adaptively biased molecular dynamics

Membrane proteins play essential roles in various biological functions within the cell. One of the most common functional regulations involves the dimerization of two single-pass transmembrane (TM) helices. Glycophorin A (GpA) and amyloid precursor protein (APP) form TM homodimers in the membrane, which have been investigated both experimentally and computationally. The homodimer structures are well characterized using only four collective variables (CVs) when each TM helix is stable. The CVs are the interhelical distance, the crossing angle, and the Crick angles for two TM helices. However, conformational sampling with multi-dimensional replica-exchange umbrella sampling (REUS) requires too many replicas to sample all the CVs for exploring the conformational landscapes. Here, we show that the bias-exchange adaptively biased molecular dynamics (BE-ABMD) with the four CVs effectively explores the free-energy landscapes of the TM helix dimers of GpA, wild-type APP and its mutants in the IMM1 implicit membrane. Compared to the original ABMD, the bias-exchange algorithm in BE-ABMD can provide a more rapidly converged conformational landscape. The BE-ABMD simulations could also reveal TM packing interfaces of the membrane proteins and the dependence of the free-energy landscapes on the membrane thickness. This approach is valuable for numerous other applications, including those involving explicit solvent and a lipid bilayer in all-atom force fields or Martini coarse-grained models, and enhances our understanding of protein-protein interactions in biological membranes.

Free Energy Barriers for Passive Drug Transport through the Mycobacterium tuberculosis Outer Membrane: A Molecular Dynamics Study.

The emergence of multi-drug-resistant tuberculosis strains poses a significant challenge to modern medicine. The development of new antituberculosis drugs is hindered by the low permeability of many active compounds through the extremely strong bacterial cell wall of mycobacteria. In order to estimate the ability of potential antimycobacterial agents to diffuse through the outer mycolate membrane, the free energy profiles, the corresponding activation barriers, and possible permeability modes of passive transport for a series of known antibiotics, modern antituberculosis drugs, and prospective active drug-like molecules were determined using molecular dynamics simulations with the all-atom force field and potential of mean-force calculations. The membranes of different chemical and conformational compositions, density, thickness, and ionization states were examined. The typical activation barriers for the low-mass molecules penetrating through the most realistic membrane model were 6-13 kcal/mol for isoniazid, pyrazinamide, and etambutol, and 19 and 25 kcal/mol for bedaquilin and rifampicin. The barriers for the ionized molecules are usually in the range of 37-63 kcal/mol. The linear regression models were derived from the obtained data, allowing one to estimate the permeability barriers from simple physicochemical parameters of the diffusing molecules, notably lipophilicity and molecular polarizability.

Molecular Simulation Studies on the Vapor-Liquid Equilibrium of CO2 + 3,3,3-Trifluoropropene (R1243zf) Binary Mixtures.

As fourth-generation refrigerants with great development prospects, hydrofluoroolefins (HFOs) can be mixed with other refrigerants, such as carbon dioxide (CO2), to form refrigerant mixtures with low global warming potential (GWP) and zero ozone depleting potential (ODP) while retaining the advantages of each component. Refrigerants can work together to achieve complementary benefits. Combinations of CO2 and HFOs can strengthen the thermodynamic properties of CO2 while inhibiting the flammability of HFOs. At present, relatively few studies have been conducted on the CO2 + 3,3,3-trifluoropropene (R1243zf) mixture. Besides experimental approaches, molecular simulation has grown in importance as a way to determine thermodynamic and transport properties in recent years. In this study, the Gibbs Ensemble Monte Carlo (GEMC) method was used to simulate the vapor-liquid equilibrium (VLE) properties of the CO2 + R1243zf binary mixture in the temperature range of 273.15 to 313.15 K, in which the three-site rigid TraPPE force field and a fully flexible transferable all-atom force field were selected to describe CO2 and R1243zf, respectively. By comparing the GEMC simulation results with the experimental data, it was found that the average deviation of pressure is 2.33%, the average deviation of liquid phase molar fraction Δx is 0.0099, and the mean deviation of gaseous phase molar fraction Δy is 0.0204. The simulation results accord well with the experimental data and the fitting data of the correlation model in the literature, indicating that the molecular models used for CO2 and R1243zf can reliably predict the VLE properties. Finally, the critical parameters of the mixture at a temperature of 313.15 K were predicted, and the radial distribution functions (RDFs) of pure R1243zf and the mixture at 273.15 K and 3.5 MPa were calculated and analyzed by molecular dynamics (MD) simulation.

Study of field ion emission from ionic liquids using molecular dynamics simulations

Molecular dynamics simulations are employed to study the field ion emission from ionic liquids. Here, an all-atom polarizable force field is selected to model the ionic liquid 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIM BF4). This force field presents a superior ability to reproduce the transport properties of the liquid, and it is used for the first time in the analysis of field ion emission. Initially, the case of a suspended droplet of ionic liquid is employed to describe the characteristics of the liquid at equilibrium. Then, a simulation comprising a nano-droplet of ionic liquid attached to a wall and exposed to a uniform electric field is employed to study the emission of ions. The current emitted, the beam composition, the energy deficit, and the mean characteristics of the process are reported. An extensive analysis is then carried out based on the process characteristics, the theory of field evaporation, and previous numerical solutions. The results suggested that steady field evaporation is unlikely to take place in most of the cases simulated. Field evaporation appears to be limited to the use of low electric fields, which makes the rate of emission decrease significantly. Despite this limitation, insights are made regarding the role of droplet polarization in decreasing the vaporization energy of the ions. The emission process observed in the simulations seems to be related to the stability limit of the droplet and the tearing of its surface, resembling a periodic jet-type of emission.

Accurately simulating electrical double layers structure and formation using all-atom scaled-charge force fields

This study revealed that the all-atom scaled-charge force field could more accurately simulate charge storage and charging dynamics of the electric double layers compared to other force fields.