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In the field of molecular simulation for drug design, traditional molecular mechanic force fields and quantum chemical theories have been instrumental but limited in terms of scalability and computational efficiency. To overcome these limitations, machine learning force fields (MLFFs) have emerged as a powerful tool capable of balancing accuracy with efficiency. MLFFs rely on the relationship between molecular structures and potential energy, bypassing the need for a preconceived notion of interaction representations. Their accuracy depends on the machine learning models used, and the quality and volume of training data sets. With recent advances in equivariant neural networks and high‐quality datasets, MLFFs have significantly improved their performance. This review explores MLFFs, emphasizing their potential in drug design. It elucidates MLFF principles, provides development and validation guidelines, and highlights successful MLFF implementations. It also addresses potential challenges in developing and applying MLFFs. The review concludes by illuminating the path ahead for MLFFs, outlining the challenges to be overcome and the opportunities to be harnessed. This inspires researchers to embrace MLFFs in their investigations as a new tool to perform molecular simulations in drug design. [ABSTRACT FROM AUTHOR]

Motivated by the problem of optimization of force-field systems in physics using large-scale computer simulations, we consider exploration of a deterministic complex multivariate response surface. The objective is to find input combinations that generate output close to some desired or “target” vector. Despite reducing the problem to exploration of the input space with respect to a 1-D loss function, the search is nontrivial and challenging due to infeasible input combinations, high dimensionalities of the input and output space and multiple “desirable” regions in the input space, and the difficulty of emulating the objective function well with a surrogate model. We propose an approach that is based on combining machine learning techniques with smart experimental design ideas to locate multiple good regions in the input space. Note to Practitioners—ReaxFF is a force field that incorporates complex functions with associated inputs in order to describe the inter- and intra-atomic interactions in materials systems. A typical ReaxFF force field consists of hundreds of parameters (inputs) per element type. During the development of a force field for a molecular system of interest, using computer simulations, these parameters are optimized to reproduce hundreds of material properties close to some benchmark reference values. Finding “good” combinations of hundreds of parameters that produce hundreds of reference values close to their gold standards is a challenging problem because there may be several parameter combinations that may be “almost equally good” or “equally desirable.” To add to the complication, several input combinations simply lead to a system crash, not producing any output at all. Standard global optimization methods do not address such a problem. We propose a novel framework that can address this problem. Beyond the ReaxFF optimization, it can be applied to multiobjective optimization in engineering and the physical sciences, where there are unknown constraints and the focus is on obtaining several good points that can serve as alternatives to a single global optimum. [ABSTRACT FROM AUTHOR]

A new set of Lennard–Jones parameters to account the short interactions between atoms of MOFs and of guest molecules is proposed. The Slater‒Kirkwood relationship was used to obtain the LJ parameters for the framework atoms, so the proposed force set of parameters was named the Slater–Kirkwood force field (SKFF). GCMC simulations using SKFF were performed to predict the adsorption of CO2, CH4 and linear alkanes on several IRMOFs. The results predicted by SKFF were compared to those obtained by the traditional general force fields used in screening MOFs (UFF and Dreiding). The performance of the proposed SKFF was superior to those of the UFF and Dreiding force fields, without accounting electrostatic contributions. Additionally, the proposed set of parameters was able to accurately predict the adsorption behavior of binary (CO2–CH4, CO2–N2, CH4–N2) and ternary (N2–CO2–CH4) mixtures on IRMOF-1 at 297 K. To evaluate the transferability of SKFF to other MOFs, the adsorption isotherms of CO2, CH4 and N2 on UiO-66, UiO-67, DUT-52, CuBTC, MIL-100(Cr), MIL-47(V), ZIF-8 and ZIF-97 were also predicted. The results presented good agreement with the experimental data. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • The main cysteine protease (Mpro) of coronavirus SARS-CoV-2 is a promising target. • Benchmarking six MD force fields, such as (OPLS-AA, CHARMM27, CHARMM36, AMBER03, AMBER14SB and GROMOS G54A7, is performed. • Native fold of monomeric and dimeric Mpro is considered. • Tertiary structure and the inter-residue distance between the catalytic dyad His41-Cys145 as key parameters. [ABSTRACT FROM AUTHOR]

Bonded (or valence) interactions, which directly determine the local structures of the molecules, are fundamental parts of molecular mechanics force fields (FFs). Most popular classical FFs adopt the simple harmonic models for bond stretching and angle bending and ignore cross-coupling effects among the valence terms. This may lead to less accurate vibrational properties and configurations in molecular dynamics (MD) simulations. AMOEBA models utilize an MM3(MM4)-style bonded interaction model, in which the vibrational anharmonicity, the coupling effects among different energy terms, and the out-of-plane bending for sp2-hybridized atoms are considered. In this work, we report the development of bonded interaction parameters for a wide range of chemistry based on quantum mechanics (QM). About 270 atomic types defined by SMARTS strings were used to model the valence interactions. Our results indicate that the resulting valence parameters produce accurate vibrational frequencies (RMSD from QM is less than ∼36.6cm−1) over a large set of molecules with diverse functional groups (445 molecules). By contrast, the harmonic models usually give an RMS error greater than 60cm−1. Meanwhile, this model accurately reflects the potential energy surface of the out-of-plane bending. Our model can generally be applied to the AMOEBA family and any MM3(MM4)-based molecular mechanics FFs. Bonded interactions are fundamental ingredients of molecular mechanics force fields because they directly determine the local structure of a molecule. In this work, we parametrize the advanced bonded energy functionals that consider the vibrational anharmonicity, the coupling effects, and the out-of-plane bending for sp2-hybridized atoms. It is expected that these models can describe the spectroscopic properties and overall structures of a molecule more accurately when they are used with polarizable AMOEBA-based force fields. [ABSTRACT FROM AUTHOR]

Molecular mechanics force field calculations have historically shown significant limitations in modeling the energetic and conformational interconversions of highly substituted furanose rings. This is primarily due to the gauche effect that is not easily captured using pairwise energy potentials. In this study, we present a refinement to the set of torsional parameters in the General Amber Force Field (gaff) used to calculate the potential energy of mono, di-, and gem-fluorinated nucleosides. The parameters were optimized to reproduce the pseudorotation phase angle and relative energies of a diverse set of mono- and difluoro substituted furanose ring systems using quantum mechanics umbrella sampling techniques available in the IpolQ engine in the Amber suite of programs. The parameters were developed to be internally consistent with the gaff force field and the TIP3P water model. The new set of angle and dihedral parameters and partial charges were validated by comparing the calculated phase angle probability to those obtained from experimental nuclear magnetic resonance experiments. [ABSTRACT FROM AUTHOR]

Molecular dynamics (MD) simulation is a powerful tool for exploring the conformational energy landscape of proteins, and the reliability of MD results is crucially dependent on the underlying force field (FF). An accurate FF capable of producing balanced distributions of diverse conformations at multiple levels has been a long‐sought goal. Towards this, several decades of joint efforts have been made to address FF deficiencies, manifested by conformational biases at different levels (local conformations, secondary structures, and global extendedness of polypeptide chain). We first present the major FF biases, then review the strategies to address them separately. Specifically, both nonresidue‐specific and residue‐specific strategies for torsional parameter optimization have been applied to achieve local conformation and secondary structure balances. Significant improvements can be gained with residue‐specific torsional parameters especially when explicit dihedral couplings are considered. Further, the additional balance between protein–protein and protein–water interactions has been optimized via multiple ways to reproduce the global extendedness of polypeptide chains, especially for unfolded or disordered proteins. This review aims to summarize the most valuable experience and lessons gained from the past, which, we hope, can facilitate further improvements of both classical FFs and more sophisticated models such as polarizable FFs. This article is categorized under:Molecular and Statistical Mechanics > Molecular Dynamics and Monte‐Carlo MethodsMolecular and Statistical Mechanics > Molecular Mechanics [ABSTRACT FROM AUTHOR]

Hexagonal boron nitride (hBN), a promising 2D nanomaterial, has potential applications in desalination and osmotic energy harvesting. In all these applications, surface roughness significantly impacts fluid flow in nanomaterial, but its precise effect remains unclear. This creates a knowledge gap in understanding how surface roughness influences water flow at the water-hBN interface, which hinders the development of accurate molecular dynamics (MD) simulations. Here, we address this gap by employing density functional theory (DFT) to calculate atomic charges on rough hBN surfaces. These charges are incorporated into MD simulations, revealing a strong influence on the water-hBN interface. This combined approach accurately predicts experimental water slip length. We further quantify the water flow behavior on hBN using established force fields. Incorporating surface roughness into the model yields results in close agreement with the experimental slip length of ∼ 1 nm for water using FF-2 force fields, validating the simulation approach. Our findings highlight the importance of incorporating realistic surface roughness and force field models in MD simulations of water-nanomaterial interfaces. This work underscores the critical role of accurate 2D material models for understanding fluid flow in nanofluidic applications. [Display omitted] • Surface roughness accurately predicts water slip length (∼ 1 nm) on hBN. • Surface roughness increases friction and reduces slip length on hBN. • Potential to tailor slip length by manipulating roughness. • Close agreement with the experimental slip length of ∼ 1 nm using FF-2 force fields. • Study enhances understanding of nanoscale friction at water-hBN interfaces. [ABSTRACT FROM AUTHOR]

In the present manuscript, a mathematical model of steady and incompressible Casson fluid in a non-uniform tube having many stenoses in the presence of a force field is analyzed. Using mild stenosis approximation and appropriate boundary conditions, analytical expressions for velocity, pressure drop, impedance, and wall share stress have been computed due to their importance in the rheology of blood. The Casson fluid is used to depict the behavior of blood flow. The effects of different physical constraints on resistance to the flow and wall shear stress of the fluid are examined. The study ascertains that resistance to the flow and wall shear stress is maximum at duck of stenosis. It is also explored that an increase in the size of the stenosis in the artery affects the normal flow of the blood through vessels in the heart, body, and brain and this may lead to major cardiac disease problems like stroke, heart attack, etc. [ABSTRACT FROM AUTHOR]

The ability to automatically extend and improve molecular force fields to accurately describe an ever wider range of compounds is a key enabler for the application of molecular modelling of chemicals and materials in industry. In this work we have developed a set of tools to process structural data available in well-known databases, to find deficiencies in the force field, and where necessary, automatically fit force- field parameters to on-the-fly calculated quantum data based on Density Functional Theory, supplemented by experimental data. The protocols have been applied to structures from the Maybridge, PoLyInfo and ILThermo databases, covering drug-like molecules, polymers and ionic liquids respectively. We demonstrate that the new version of the force field can type all structures in the extended data set without missing parameters, with a similar high-quality prediction of geometry (bonds, angles, torsions), energy and forces of earlier versions. [ABSTRACT FROM AUTHOR]

[Display omitted] • Anhydrous, mono, di and trihydrate species were studied by using DFT calculations. • Mapped MEP surfaces show increase in the energies values from anhydrous to trihydrate. • Complete vibrational assignments of all the species are reported. • NBO studies reveal that the trihydrate in the gas phase is the most stable species. • The dihydrate is the most reactive species in gas phase and the anhydrous in solution. Theoretical structures of anhydrous (A), mono (M), di (D) and trihydrate (T) species of bronchodilator theophylline agent have been studied by using hybrid B3LYP/6–311++G** calculations to analyse the role of water molecules in its properties, reactivities and behaviours. The dipole moments increase with the number of water molecules (N) while the volumes (V) and solvation energies evidence behaviours lineal with N. D species shows higher V contraction, as T while A and M show slight V expansions. MEP surfaces show increase in energy from A to T. NBO studies reveal that T is most stable in the gas phase while A in solution. Gap values show that D is the most reactive species in gas phase while A in solution. Complete assignments of all the species and their scaled force constants are reported including librations of water molecules. [ABSTRACT FROM AUTHOR]

Flavin containing molecules form a group of important cofactors that assist a wide range of enzymatic reactions. Flavins use the redox‐active isoalloxazine system, which is capable of one‐ and two‐electron transfer reactions and can exist in several protonation states. In this work, molecular mechanics force field parameters compatible with the CHARMM36 all‐atom additive force field were derived for biologically important flavins, including riboflavin, flavin mononucleotide, and flavin adenine dinucleotide. The model was developed for important protonation and redox states of the isoalloxazine group. The partial charges were derived using the CHARMM force field parametrization strategy, where quantum mechanics water–solute interactions are used to target optimization. In addition to monohydrate energies and geometries, electrostatic potential around the compound was used to provide additional restraints during the charge optimization. Taking into account the importance of flavin‐containing molecules special attention was given to the quality of bonded terms. All bonded terms, including stiff terms and torsion angle parameters, were parametrized using exhaustive potential energy surface scans. In particular, the model reproduces well the butterfly motion of isoalloxazine in the oxidized and reduced forms as predicted by quantum mechanics in gas phase. The model quality is illustrated by simulations of four flavoproteins. Overall, the presented molecular mechanics model will be of utility to model flavin cofactors in different redox states. © 2019 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The parametrization of classical nonbonded models of metal ions has been widely addressed in the recent years. Despite the continuous development of novel and more physically inspired functional forms, the 12‐6 Lennard‐Jones plus Coulomb potential is still the most adopted force field in molecular dynamics (MD) codes, owing to its simple form and easy implementation. However, due to the integer formal charge, unpolarizable force fields of ions may suffer from overestimated interatomic electrostatic interactions, leading to nonphysical clustering or repulsion between such full charges. The electronic continuum correction (ECC) can fix this problem through a simple inclusion of solvent polarization effects via ionic charge rescaling. In this work, the development of novel nonbonded models for mono, divalent, and highly charged metal ions is presented. For each metal species, the ionic charge has been scaled, according to the ECC. Lennard‐Jones parameters have been optimized using experimental structural and thermodynamic properties as target quantities. Performances of the proposed models are discussed and compared with the literature data, while transferability attitudes among different and well‐known water models are evaluated. © 2019 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Valence Shell Electron Pair Repulsion (VSEPR) theory, commonly taught in introductory chemistry courses, provides a basis for understanding the molecular structures of molecules of the type XY , where X is a central atom surrounded by m Y ligands. While VSEPR is generally thought of only as a qualitative theory, Bartell and coworkers constructed a semi-quantitative model potential to address the physical underpinnings of VSEPR by introducing a points-on-a-sphere (POS) potential such that all X-Y bonds are of fixed length and all atoms Y repel each other. More than forty years ago, this simple model was shown to be effective in reproducing relative quadratic and cubic bending force constants for a variety of binary XY compounds when compared to values computed with semi-empirical and fairly primitive methods. The work presented here endeavours to go beyond the model used in the early investigations by Bartell and coworkers. Specifically, stretching force constants are clearly omitted from any POS model with a fixed radius, and are (primitively) included here by treating all X-Y bonds as simple (and equivalent) Morse oscillators. With the additional degrees of freedom in the parametrization that come from the Morse potential, the resulting model was investigated. The degree to which this simple mechanical model can reproduce quadratic and cubic force fields for PF is studied here, as well as how it works for a more difficult problem – the energetics and transition state properties for the intermediate in the (Berry) pseudorotation process that interchanges axial and equatorial fluorines in this prototype molecule. The five parameter Morse-POS model is shown to be do quite well in describing the quadratic and cubic force fields, as well as the pseudorotation process, a fairly impressive feat given the naivete of the model. [ABSTRACT FROM AUTHOR]

Valence Shell Electron Pair Repulsion (VSEPR) theory, commonly taught in introductory chemistry courses, provides a basis for understanding the molecular structures of molecules of the type XY , where X is a central atom surrounded by m Y ligands. While VSEPR is generally thought of only as a qualitative theory, Bartell and coworkers constructed a semi-quantitative model potential to address the physical underpinnings of VSEPR by introducing a points-on-a-sphere (POS) potential such that all X-Y bonds are of fixed length and all atoms Y repel each other. More than forty years ago, this simple model was shown to be effective in reproducing relative quadratic and cubic bending force constants for a variety of binary XY compounds when compared to values computed with semi-empirical and fairly primitive methods. The work presented here endeavours to go beyond the model used in the early investigations by Bartell and coworkers. Specifically, stretching force constants are clearly omitted from any POS model with a fixed radius, and are (primitively) included here by treating all X-Y bonds as simple (and equivalent) Morse oscillators. With the additional degrees of freedom in the parametrization that come from the Morse potential, the resulting model was investigated. The degree to which this simple mechanical model can reproduce quadratic and cubic force fields for PF is studied here, as well as how it works for a more difficult problem – the energetics and transition state properties for the intermediate in the (Berry) pseudorotation process that interchanges axial and equatorial fluorines in this prototype molecule. The five parameter Morse-POS model is shown to be do quite well in describing the quadratic and cubic force fields, as well as the pseudorotation process, a fairly impressive feat given the naivete of the model. [ABSTRACT FROM AUTHOR]

We propose a general strategy to remediate force‐field artifacts in describing pairwise interactions among similar molecules M in the vicinity of another chemical species, C, like water molecules interacting at short distance from a monoatomic ion. This strategy is based on introducing a three‐body potential energy term that alters the pairwise interactions among M‐type molecules when they lie at short range from the species C. In other words the species C is the center of a space domain where the pairwise interactions among the molecules M is altered. Here, we apply it to improve the description of the water interactions provided by the polarizable water model TCPE/2013 in the vicinity of halides, from F− to At−, and of the prototypical carboxylate anion CH3COO−. We show the accuracy and the transferability of such an approach to investigate not only the hydration process of single anions but also of a salt solution NH4+/Cl‐ in aqueous phase. This strategy can be used to remediate the drawbacks of any kind of force fields. © 2019 Wiley Periodicals, Inc. A general strategy is proposed to remediate force‐field artifacts in describing solvent pairwise interactions in the vicinity of a solute, based on introducing a three‐body potential energy term that alters the solvent pairwise interactions in a space domain centered at the solute. It is used to improve the description of the water interactions provided by the polarizable water model TCPE/2013 in the vicinity of halides, from F− to At−, and of the carboxylate anion CH3COO−. [ABSTRACT FROM AUTHOR]

Abstract FT-IR, FT-Raman and ultraviolet–visible spectroscopies were used to characterize the potassium 5-hydroxypentanoyltrifluoroborate salt (HTFB) while the theoretical structures of this salt in gas and aqueous solution phases were studied by using hybrid B3LYP/6-311++G** calculations and the self consistent reaction field (SCRF) and solvation (SM) models because these models consider the solvent effects. Good concordance were obtained among the predicted 1H-, 13C and 19F-NMR chemical shifts for HTFB in aqueous solution with the corresponding experimental available data for this salt in CDCl 3. The corrected solvation energy by using ZPVE and non electrostatic terms is higher for this salt (−103.73 kJ/mol) than those reported for furoyl (−84.72 kJ/mol) and isonicotinoyl (−95.05 kJ/mol). Evidently, the side chain in HTFB increase the solubility of this salt in water, as compared with furoyl and isonicotinoyl. The NBO analyses show that the potassium 2-isonicotinoyltrifluorborate salt in both media is most stable than hydroxypentanoyl and furoyl salts and, in particular, the side chain in HTFB generates a diminishing of its stability in aqueous solution. Probably, this low stability of HTFB in solution is due to the higher solvation energy and to the n→σ∗ transitions no observed in the other salts. The AIM studies support the high stability of isonicotinoyl than the other two salts and, also, reveal the ionic characteristics of the K --O and K --F interactions observed in those three salts. The comparisons of the gap values for the three species suggest that the most reactive salt is isonicotinoyl while furoyl salt is the less reactive. The descriptors show the importance of study these salts in different media because the values in solution are slightly different in the three salts from those computed in gas phase. In addition, the harmonic force fields and the scaled internal force constants for the salt in both media are reported together to their complete vibrational assignments. Graphical abstract Image 1 Highlights • HTFB was characterized by FT-IR, FT-Raman and UV–Vis spectroscopies. • The HTFB structure was studied by using hybrid B3LYP/6-311++G** calculations. • The corrected solvation energy is higher in HTFB than the FTFB and ITFB salts. • The NBO analyses show that the side chain in HTFB decrease its stability in solution. • The AIM reveal the ionic characteristics of the Ke--O and Ke--F interactions. [ABSTRACT FROM AUTHOR]

Abstract A β -amyloid self-assembly is related to the changing the structure of the β -amyloid from the helix to the sheet. This structural change is one of the main reasons for developing Alzheimer's disease. Usually, the addition of non-polar solvents to water is used to study the role of hydrophobic forces in the self-assembly behavior. However, adding non-polar solvents also causes unwanted structural changes. Here, by changing the Lennard-Jones potential repulsion expression, structural changes in Amyloid β -peptide (1-40) (A β 40) have been studied using molecular dynamics simulation. For this purpose, in the Lennard-Jones potential n = 6 and m = 8 , 9, 10, 11, 12 were placed in attractive and repulsion terms, respectively. Then this change in the potential was applied to the GROMOS96 and OPLS-AA/L force fields. Molecular dynamics simulations of A β 40 were performed based on these 10 potentials. The results show that the change in the Lennard-Jones repulsion term in both of the applied force fields does not have a regular impact on the structure and dynamics of the A β 40. For example, with the change of m = 12 to m = 11 in the GROMOS96 force field, the diffusion coefficient of A β 40 decreases, while with the change of m = 11 to m = 10, the diffusion coefficient increases in this force field. The change zones in the secondary and tertiary structures are also different. However, the results indicate that the OPLS AA/L force field is more sensitive to the change in the Lennard-Jones potential repulsion term. Highlights • A new method was presented for studying A β -amyloid self-assembles. • The change zones in the secondary and tertiary structures are different. • The percentage of turn secondary structure in the LJ 6-12 has the highest value. • Sensitivity of the OPLS-AA/L force field to the potential change is more. [ABSTRACT FROM AUTHOR]

Refinement is the last step in protein structure prediction pipelines to convert approximate homology models to experimental accuracy. Protocols based on molecular dynamics (MD) simulations have shown promise, but current methods are limited to moderate levels of consistent refinement. To explore the energy landscape between homology models and native structures and analyze the challenges of MD-based refinement, eight test cases were studied via extensive simulations followed by Markov state modeling. In all cases, native states were found very close to the experimental structures and at the lowest free energies, but refinement was hindered by a rough energy landscape. Transitions from the homology model to the native states require the crossing of significant kinetic barriers on at least microsecond time scales. A significant energetic driving force toward the native state was lacking until its immediate vicinity, and there was significant sampling of off-pathway states competing for productive refinement. The role of recent force field improvements is discussed and transition paths are analyzed in detail to inform which key transitions have to be overcome to achieve successful refinement. [ABSTRACT FROM AUTHOR]

The analysis of remote sensing (RS) images, which is often accomplished using unsupervised image classification techniques, requires an effective method to determine an appropriate number of classification clusters. This paper proposes a preliminary analytical method to evaluate the input parameters for unsupervised RS image classification. Our approach involves first analysing the colour spaces of RS images based on the human visual perception theory. This enables the initial number of clusters and their corresponding centres to be automatically established based on the interaction of different forces in our supposed force field. The proposed approach can automatically determine the appropriate initial number of clusters and their corresponding centres for unsupervised image classification. A comparison of the experimental results with those of existing methods showed that the proposed method can considerably facilitate unsupervised image classification for acquiring accurate results efficiently and effectively without any prior knowledge. [ABSTRACT FROM AUTHOR]

Molecular dynamics simulations are employed to investigate the aggregation behavior at the late stages of silica production in a colloidal solution to find new insights into the structures and dynamics of the produced aggregates and pores. The implemented theoretical investigations used the Amorphous cell and Forcite modules, and Dreiding force field of Materials Studio package. The key thermodynamic parameters, mean squared displacements, and radial distribution functions were calculated. Results revealed that aggregation occurred in the late stages due to the negative value of Gibbs free energy. Diameters of the generated “aggregates and pores” continuously increased while the number of “aggregates and pores” first increased and then decreased. Furthermore, the volume of pores first rose and then fell as the reaction proceeded. Variations of reactant numbers had the noticeable influence on the pores and aggregates topologies. The number of aggregates and pores had an upward trend while their diameters slightly reduced when more effective molecules were involved in the aggregation process. In addition, the shape of the aggregates examined and found that the predominant shapes of the aggregates were spherical. [ABSTRACT FROM AUTHOR]

The optimisation of a peptide-capped glycine using the novel force field FFLUX is presented. FFLUX is a force field based on the machine-learning method kriging and the topological energy partitioning method called Interacting Quantum Atoms. FFLUX has a completely different architecture to that of traditional force fields, avoiding (harmonic) potentials for bonded, valence and torsion angles. In this study, FFLUX performs an optimisation on a glycine molecule and successfully recovers the target density-functional-theory energy with an error of 0.89 ± 0.03 kJ mol−1. It also recovers the structure of the global minimum with a root-mean-squared deviation of 0.05 Å (excluding hydrogen atoms). We also show that the geometry of the intra-molecular hydrogen bond in glycine is recovered accurately. [ABSTRACT FROM AUTHOR]

Abstract: Structural characterization of liquid pyrrole has been obtained by performing classical molecular dynamics simulations with a new parameterization of electrostatic interactions. Despite the relatively simple molecular structure of pyrrole, a correct and accurate representation of its intermolecular interactions in bulk phase is a challenging task, since these are affected at short range by the quadrupole–quadrupole term. This new parameterization permits not only to correctly describe the liquid structure but also to obtain macroscopic properties in excellent agreement with experiments. [ABSTRACT FROM AUTHOR]

Molecular dynamics (MD) simulation has become a powerful tool for characterizing at an atomic level of detail the conformational changes undergone by proteins. The application of such simulations to RNA structures, however, has proven more challenging, due in large part to the fact that the physical models ("force fields") available for MD simulations of RNA molecules are substantially less accurate in many respects than those currently available for proteins. Here, we introduce an extensive revision of a widely used RNA force field in which the parameters have been modified, based on quantum mechanical calculations and existing experimental information, to more accurately reflect the fundamental forces that stabilize RNA structures. We evaluate these revised parameters through long-timescale MD simulations of a set of RNA molecules that covers a wide range of structural complexity, including single stranded RNAs, RNA duplexes, RNA hairpins and riboswitches. The structural and thermodynamic properties measured in these simulations exhibited dramatically improved agreement with experimentally determined values. Based on the comparisons we performed, this RNA force field appears to achieve a level of accuracy comparable to that of state-of-the-art protein force fields, thus significantly advancing the utility of MD simulation as a tool for elucidating the structural dynamics and function of RNA molecules and RNA containing biological assemblies. [ABSTRACT FROM AUTHOR]

Carquejol and its acetate are monoterpenoids based on the rare o -menthane skeleton and distinctive components of the essential oil from Baccharis trimera . Carquejol was characterized by using Fourier Transform infrared (FT-IR) and Raman (FT-Raman), Ultraviolet–Visible (UV–Visible), Electronic Circular Dichroism (ECD), Mass, Hydrogen and Carbon Nuclear Magnetic Resonance ( 1 H and 13 C NMR) and 2D 1 H 1 H gCOSY, 1 H 13 CgHSQC, 1 H 13 CgHMBC spectroscopies. Due to the chirality of this monoterpenoid, six different structures were analysed, of which only four showed higher populations and minimal energies. The natural bond orbital (NBO), atoms in molecules (AIM), Merz-Kollman (MK) charges, molecular electrostatic potentials (MEP) and frontier orbitals studies were performed in order to evaluate their structural, electronic, topological and vibrational properties. All calculations were performed by using the hybrid B3LYP method and the 6-31G* and 6-311++G** basis sets. The comparison of the experimental ECD spectra with the corresponding theoretical ones confirm the (4S,5R) configuration assigned to carquejol. The force fields for the most stable configurations were computed by using those two levels of theory and the complete vibrational assignments for the two conformations of carquejol are reported. The different orientations and directions of the dipole moments of the two structures and the proximity in the nucleophilic indexes with those reported for other terpenes could justify in part the potential biological properties reported for carquejol. The MEP surfaces for both structures reveal that the nucleophilic and electrophilic sites of higher reactivity are principally centred on the OH groups. [ABSTRACT FROM AUTHOR]

By combining the bottom-up and top-down approaches, we have developed a new all-atom (AA) force field from quantum mechanics and experimental data and a new coarse grained (CG) force field from AA simulation and experimental data, for polydimethylsiloxane (PDMS). The AA force field is developed based on the TEAM force field database. The CG force field uses a mapping rule that splits the connecting oxygen into neighbouring CG beads to maintain the charge neutrality of the beads, analytical functional forms including anharmonic terms in the valence terms, and the temperature-dependent free-energy functional form to describe the inter-bead interactions. Broad range of thermodynamic properties of PDMS including density, surface tension, solubility parameter, radius of gyration and glass transition temperature are calculated to validate the force fields, and good agreements with the experimental data are obtained. [ABSTRACT FROM PUBLISHER]

To study the microscopic thermal aging mechanism of insulating paper cellulose through molecular dynamics simulation, it is important to select suitable DP (Degree of Polymerization) and force field for the cellulose model to shorten the simulation time and obtain correct and objective simulation results. Here, the variation of the mechanical properties and solubility parameters of models with different polymerization degrees and force fields were analyzed. Numerous cellulose models with different polymerization degrees were constructed to determine the relative optimal force field from the perspectives of the similarity of the density of cellulose models in equilibrium to the actual cellulose density, and the volatility and repeatability of the mechanical properties of the models through the selection of a stable polymerization degree using the two force fields. The results showed that when the polymerization degree was more than or equal to 10, the mechanical properties and solubility of cellulose models with the COMPASS (Condensed-phase Optimized Molecular Potential for Atomistic Simulation Studies) and PCFF (Polymer Consistent Force Field) force fields were in steady states. The steady-state density of the cellulose model using the COMPASS force field was closer to the actual density of cellulose. Thus, the COMPASS force field is favorable for molecular dynamics simulation of amorphous cellulose. [ABSTRACT FROM AUTHOR]

The paper deals with the development and subsequent testing of a Buckingham interaction potential which allows one to correctly describe the atom-by-atom growth of TiO 2 . Contrary to the most frequent procedures of the interaction potential development, correct coordination numbers which the potential leads to in an open surface growth are included amongst the criteria of success. First, parameters describing the short-range interaction have been fitted in order to achieve correct lattice parameters and formation energies in a wide range of Ti and O elemental charges. Next, growth simulations of amorphous TiO 2 have been performed in order to investigate and quantify the relationship between the elemental charges and the preferred coordination numbers. The interaction potential which leads to the most experimentally relevant structures (in terms of coordination numbers) has been identified. This potential was further tested by growth simulations of crystalline TiO 2 . [ABSTRACT FROM AUTHOR]

The fully polarizable, multipolar, and atomistic force field protein FFLUX is being built from machine learning (i.e., kriging) models, each of which predicts an atomic property. Each atom of a given protein geometry needs to be assigned such a kriging model. Such a knowledgeable atom needs to be informed about a sufficiently large environment around it. The resulting complexity can be tackled by collecting the 20 natural amino acids into a few groups. Using substituted deca-alanines, we present the proof-of-concept that a given atom's charge can be modeled by a few kriging models only. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Drug-like ligands obtained from protein-ligand complexes deposited in the Protein Databank were subjected to conformational searching using various force fields and solvation settings. For each ligand, the resulting conformer pool was examined for the presence of the bioactive (crystal pose-like) conformation. Similarity of conformers toward the crystal-pose was quantified as the best achievable root mean squared deviation (RMSD, heavy atoms only). Analyzing the conformer pools generated by various force fields revealed only small differences in the likelihood of finding a crystal pose-like conformation. However, employing different solvents in the conformational search was found to be very important for achieving RMSDs below 1.0 Å. The best statistical values of likelihood were observed with a recently released force field covering a large portion of dihedral angles occurring in drug-like compounds in combination with the water as solvent. In order to enable computational chemists and modelers to efficiently use available software tools, we have additionally performed several focused analyses on ligands, grouped according to descriptors most relevant for the rational drug design. [ABSTRACT FROM AUTHOR]

The force field conversion from one MD program to another one is exhausting and error-prone. Although single conversion tools from one MD program to another exist not every combination and both directions of conversion are available for the favorite MD programs A mber, C harmm, D l-P oly, G romacs, and L ammps. We present here a general tool for the force field conversion on the basis of an XML document. The force field is converted to and from this XML structure facilitating the implementation of new MD programs for the conversion. Furthermore, the XML structure is human readable and can be manipulated before continuing the conversion. We report, as testcases, the conversions of topologies for acetonitrile, dimethylformamide, and 1-ethyl-3-methylimidazolium trifluoromethanesulfonate comprising also Urey-Bradley and Ryckaert-Bellemans potentials. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

We present a systematic test of the performance of three popular united-atom force fields-OPLS-UA, GROMOS and TraPPE-at predicting hydrophobic solvation, more precisely at describing the solvation of alkanes in alkanes. Gibbs free energies of solvation were calculated for 52 solute/solvent pairs from Molecular Dynamics simulations and thermodynamic integration making use of the IBERCIVIS volunteer computing platform. Our results show that all force fields yield good predictions when both solute and solvent are small linear or branched alkanes (up to pentane). However, as the size of the alkanes increases, all models tend to increasingly deviate from experimental data in a systematic fashion. Furthermore, our results confirm that specific interaction parameters for cyclic alkanes in the united-atom representation are required to account for the additional excluded volume within the ring. Overall, the TraPPE model performs best for all alkanes, but systematically underpredicts the magnitude of solvation free energies by about 6% (RMSD of 1.2 kJ/mol). Conversely, both GROMOS and OPLS-UA systematically overpredict solvation free energies (by ∼13% and 15%, respectively). The systematic trends suggest that all models can be improved by a slight adjustment of their Lennard-Jones parameters. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

An empirical force field for carbon based upon the Murrell-Mottram potential is developed for the calculation of the vibrational frequencies of carbon nanomaterials. The potential is reparameterised using data from density functional theory calculations through a Monte-Carlo hessian-matching approach, and when used in conjunction with the empirical bond polarisability model provides an accurate description of the non-resonant Raman spectroscopy of carbon nanotubes and graphene. With the availability of analytical first and second derivatives, the computational cost of evaluating harmonic vibrational frequencies is a fraction of the cost of corresponding quantum chemical calculations, and makes the accurate atomistic vibrational analysis of systems with thousands of atoms possible. Subsequently, the non-resonant Raman spectroscopy of carbon nanotubes and graphene, including the role of defects and carbon nanotube junctions is explored. [ABSTRACT FROM AUTHOR]

Surface phenomena are increasingly becoming important in exploring nanoscale materials growth and characterization. Consequently, the need for atomistic based simulations is increasing. Recently, we proposed a machine learning approach, known as AGNI, that allows fast and quantum mechanical accurate atomic force predictions given an atom’s neighborhood environment. Here, we make use of such force fields to study and characterize the nanoscale diffusion and growth processes occurring on an Al (1 1 1) surface. In particular we focus on the adatom ripening phenomena, confirming past experimental findings, wherein a low and high temperature growth regime were observed using entirely molecular dynamics simulations. [ABSTRACT FROM AUTHOR]

One key factor that limits the predictive power of molecular dynamics simulations is the accuracy and transferability of the input force field. Force fields are challenged by heterogeneous environments, where electronic responses give rise to biologically important forces such as many-body polarisation and dispersion. The importance of polarisation in the condensed phase was recognised early on, as described by Cochran in 1959 [ Philosophical Magazine 4 (1959) 1082–1086] [32] . Currently in molecular simulation, dispersion forces are treated at the two-body level and in the dipole limit, although the importance of three-body terms in the condensed phase was demonstrated by Barker in the 1980s [ Phys. Rev. Lett. 57 (1986) 230–233] [72] . One approach for treating both polarisation and dispersion on an equal basis is to coarse grain the electrons surrounding a molecular moiety to a single quantum harmonic oscillator (cf. Hirschfelder, Curtiss and Bird 1954 [ The Molecular Theory of Gases and Liquids (1954)] [37] ). The approach, when solved in strong coupling beyond the dipole limit, gives a description of long-range forces that includes two- and many-body terms to all orders . In the last decade, the tools necessary to implement the strong coupling limit have been developed, culminating in a transferable model of water with excellent predictive power across the phase diagram. Transferability arises since the environment automatically identifies the important long range interactions, rather than the modeller through a limited set of expressions. Here, we discuss the role of electronic coarse-graining in predictive multiscale materials modelling and describe the first implementation of the method in a general purpose molecular dynamics software: QDO_MD. [ABSTRACT FROM AUTHOR]

The main goal of this work is the generation of a new force field data set to the interaction of several gases such as H2, O2, N2, CO, H2O, and H2S with alkali cation-doped carbon nanotubes (CNTs) usingab initiocalculations at the MP2(full)/6-311++G(d,p) level of theory. Different alkali cations including Li+, Na+,K+and Cs+were used to dope in the CNT. The calculated potential energy curve for the interaction of each gas molecule with each alkali cation-doped CNTs was fitted to an analytical potential function to obtain the parameters of the potential function. A modified Morse potential function was selected for the fitting in which the electrostatic interactions has been accounted by adding the β/rterm to the Morse potential. The accuracy of the calculated force field was checked via Grand Canonical Monte Carlo (GCMC) simulation of the H2adsorption on Li-doped graphite and Li-doped CNT. The results of these simulations were compared with the experimental measurements and the closeness of the simulation results with the experimental data indicated the accuracy of the proposed force field. The main merit of this work is the derivation of a specific force field for interaction of each of six gases with four alkali cation-doped CNT, which can be used in molecular simulation of these 24 of systems. The simulation results showed the increase of the H2adsorption capacity of nanotube and graphite up to 50% and 10%, respectively, due to the insertion of Li ions. [ABSTRACT FROM PUBLISHER]

Alchemical transformation of solutes using classical fixed-charge force fields is a popular strategy for assessing the free energy of transfer in different environments. Accurate estimations of transfer between phases with significantly different polarities can be difficult because of the static nature of the force fields. Here, we report on an application of such calculations in the SAMPL5 experiment that also involves an effort in balancing solute and solvent interactions via their expected static dielectric constants. This strategy performs well with respect to predictive accuracy and correlation with unknown experimental values. We follow this by performing a series of retrospective investigations which highlight the potential importance of proper balancing in these systems, and we use a null hypothesis analysis to explore potential biases in the comparisons with experiment. The collective findings indicate that considerations of force field compatibility through dielectric behavior is a potential strategy for future improvements in transfer processes between disparate environments. [ABSTRACT FROM AUTHOR]

This work presents a systematic development of a new van der Waals potential (vdW2016) for common organic molecules based on symmetry-adapted perturbation theory (SAPT) energy decomposition. The Buf-14-7 function, as well as Cubic-mean and Waldman–Hagler mixing rules were chosen given their best performance among other popular potentials. A database containing 39 organic molecules and 108 dimers was utilized to derive a general set of vdW parameters, which were further validated on nucleobase stacking systems and testing organic dimers. The vdW2016 potential is anticipated to significantly improve the accuracy and transferability of new generations of force fields for organic molecules. [ABSTRACT FROM AUTHOR]

Atomistic model has been proposed to describe the structure, phonon frequencies, and thermodynamic properties of multi-walled nanotubes based on molybdenum disulfide. [ABSTRACT FROM AUTHOR]

Atomistic model has been proposed to describe the structure, phonon frequencies, and thermodynamic properties of multi-walled nanotubes based on molybdenum disulfide. [ABSTRACT FROM AUTHOR]

Biological membranes display a great diversity in lipid composition and lateral structure that is crucial in a variety of cellular functions. Simulations of membranes have contributed significantly to the understanding of the properties, functions and behaviour of membranes and membrane–protein assemblies. This success relies on the ability of the force field used to describe lipid–lipid and lipid–environment interactions accurately, reproducibly and realistically. In this review, we present some recent progress in lipid force-field development and validation strategies. In particular, we highlight how a range of properties obtained from various experimental techniques on lipid bilayers and membranes, can be used to assess the quality of a force field. We discuss the limitations and assumptions that are inherent to both computational and experimental approaches and how these can influence the comparison between simulations and experimental data. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov. [ABSTRACT FROM AUTHOR]

The currently available force field parameters for modified RNA residues in AMBER show significant deviations in conformational properties from experimental observations. The examination of the transferability of the recently revised torsion parameters revealed that there was an overall improvement in the conformational properties for some of the modifications but the improvements were still insufficient in describing the sugar pucker preferences ( J. Chem. Inf. Model. 2014, 54, 1129-1142). Here, we report an approach for the development and fine tuning of the AMBER force field parameters for 2-thiouridine, 4-thiouridine, and pseudouridine with diverse conformational preferences. The χ torsion parameters were reparameterized at the individual nucleoside level. The effect of combining the revised γ torsion parameter and modifying the Lennard-Jones σ parameters were also tested by directly comparing the conformational preferences obtained from our extensive molecular dynamics simulations with those from experimental observations. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

This review discusses the use of molecular modeling tools, together with existing experimental findings, to provide a complete atomic-level description of enzyme dynamics and function. We focus on functionally relevant conformational dynamics of enzymes and the protonation states of substrates. The conformational fluctuations of enzymes usually play a crucial role in substrate recognition and catalysis. Protein dynamics can be altered by a tiny change in a molecular system such as different protonation states of various intermediates or by a significant perturbation such as a ligand association. Here we review recent advances in applying atomistic molecular dynamics (MD) simulations to investigate allosteric and network regulation of tryptophan synthase (TRPS) and protonation states of its intermediates and catalysis. In addition, we review studies using quantum mechanics/molecular mechanics (QM/MM) methods to investigate the protonation states of catalytic residues of β-Ketoacyl ACP synthase I (KasA). We also discuss modeling of large-scale protein motions for HIV-1 protease with coarse-grained Brownian dynamics (BD) simulations. [ABSTRACT FROM AUTHOR]

Carotenoids are important actors both in light-harvesting (LH) and in photoprotection functions of photosynthetic pigment-protein complexes. A deep theoretical investigation of this multiple role is still missing owing to the difficulty of describing the delicate interplay between electronic and nuclear degrees of freedom. A possible strategy is to combine accurate quantum mechanical (QM) methods with classical molecular dynamics. To do this, however, accurate force-fields (FF) are necessary. This article presents a new FF for the different carotenoids present in LH complexes of plants. The results show that all the important structural properties described by the new FF are in very good agreement with QM reference values. This increased accuracy in the simulation of the structural fluctuations is also reflected in the description of excited states. Both the energy order and the different nature of the lowest singlet states are preserved during the dynamics when the new FF is used, whereas an unphysical mixing is found when a standard FF is used. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Quantifying an atom's transferability, in a force field context, demands a quantitative understanding of how an atom ‘experiences’ the surrounding environment both intra-atomically and inter-atomically. Here we investigate the intra-atomic (EintraA) viewpoint through the study of the atoms Cα, Hα, N, O, and S in a series of ‘mono’-, tri- and penta-peptides. The remaining inter-atomic viewpoint consists of an electrostatic (via multipole moments), exchange and correlation components respectively, of which the electrostatic component has been previously reported. Together these four energy components, as calculated from the Interacting Quantum Atoms (IQA) partitioning approach, express the foundation of the Quantum Chemical Topological Force Field (QCTFF). In order to have transferability within a force field, smaller sample systems must be calculated and developed as representative of larger target systems. The Cα, Hα, N, O and S atoms in a tri-peptide are energetically comparable to those in their penta-peptide configurations, within 2.1 kJ/mol in absolute value (1 exception). Across all five elements, this energy difference ison average∼0.3 kJ/mol. On average, the tri-peptide sample systems represent a ∼8.2 Å atomic horizon around the central atoms of interest. Thus, both the previous knowledge of the ∼10.3 Å horizon sphere and ∼0.4 kJ/mol error required by the electrostatic multipole moments, determine how two of the four key QCTFF energy components are affected by an atom's molecular environment. [ABSTRACT FROM PUBLISHER]

This work is framed within the Eighth Industrial Fluid Properties Simulation Challenge, with the aim of assessing the capability of molecular simulation methods and force fields to accurately predict adsorption in porous media for systems of relevant practical interest. The current challenge focuses on predicting adsorption isotherms of n-perfluorohexane in the certified reference material BAM-P109 standard activated carbon. A temperature of T ¼ 273 K and pressures of p=p0 ¼ 0:1, 0.3, and 0.6 relative to the bulk saturation pressure p0 (as predicted by the model) are the conditions selected in this challenge. In our methodology we use coarse-grained intermolecular models and a top-down technique where an accurate equation of state is used to link the experimental macroscopic properties of a fluid to the force-field parameters. The state-of-the-art version of the statistical associating fluid theory (SAFT) for potentials of variable range as reformulated in the Mie group contribution incarnation (SAFT-γ Mie) is employed here. The parameters of the SAFT-γ Mie force field are estimated directly from the vapour pressure and saturated liquid density data of the pure fluids using the equation of state, and further validated by molecular dynamic simulations. The coarse-grained intermolecular potential models are then used to obtain the adsorption isotherm kernels for argon, carbon dioxide, and n-perfluorohexane in graphite slit pores of various widths using Grand Canonical Monte Carlo simulations. A unique and fluid-independent pore size distribution curve with total micropore volume of 0.5802 cm³/g is proposed for the BAM-P109. The pore size distribution is obtained by applying a non-linear regression procedure over the adsorption integral equation to minimise the quadratic error between the available experimental adsorption isotherms for argon and carbon dioxide and purpose-built Grand Canonical Monte Carlo kernels. The predicted adsorption levels of n-perfluorohexane at 273 K in BAM-P109 are 72.75±0.01, 73.82±0.01, and 75.44± 0.05 cm³/g at Standard Temperature and Pressure (STP) conditions for p=p0 ¼ 0:1, 0.3, and 0.6, respectively. [ABSTRACT FROM AUTHOR]

We introduce a simple but computationally very efficient harmonic force field, which works for all fullerene structures and includes bond stretching, bending, and torsional motions as implemented into our open-source code Fullerene. This gives accurate geometries and reasonably accurate vibrational frequencies with root mean square deviations of up to 0.05 Å for bond distances and 45.5 cm−1 for vibrational frequencies compared with more elaborate density functional calculations. The structures obtained were used for density functional calculations of Goldberg-Coxeter fullerenes up to C980. This gives a rather large range of fullerenes making it possible to extrapolate to the graphene limit. Periodic boundary condition calculations using density functional theory (DFT) within the projector augmented wave method gave an energy difference between −8.6 and −8.8 kcal/mol at various levels of DFT for the reaction C60→graphene (per carbon atom) in excellent agreement with the linear extrapolation to the graphene limit (−8.6 kcal/mol at the Perdew-Burke-Ernzerhof level of theory). © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

We introduce a simple but computationally very efficient harmonic force field, which works for all fullerene structures and includes bond stretching, bending, and torsional motions as implemented into our open-source code Fullerene. This gives accurate geometries and reasonably accurate vibrational frequencies with root mean square deviations of up to 0.05 Å for bond distances and 45.5 cm−1 for vibrational frequencies compared with more elaborate density functional calculations. The structures obtained were used for density functional calculations of Goldberg-Coxeter fullerenes up to C980. This gives a rather large range of fullerenes making it possible to extrapolate to the graphene limit. Periodic boundary condition calculations using density functional theory (DFT) within the projector augmented wave method gave an energy difference between −8.6 and −8.8 kcal/mol at various levels of DFT for the reaction C60→graphene (per carbon atom) in excellent agreement with the linear extrapolation to the graphene limit (−8.6 kcal/mol at the Perdew-Burke-Ernzerhof level of theory). © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]