Ab Initio Electrostatic Potential Research Articles

A Unified Approach to Derive Atomic Partial Charges and Polarizabilities of Ionic Liquids.

We propose a unified approach to fit simultaneously a set of atomic partial charges and polarizabilities of the polarizable model against the ab initio electrostatic potential (ESP) and polarizability. The polarizable model is represented with interactive atomic dipoles with distance-dependent attenuation. For the polarizable model employed in this study, the internal electric field on the polarization sites is fully turned on, and thus allows self-induced dipoles, which persist even for an isolated molecule/ion. By such treatment, the contribution of ESP stems not only from the partial charges but also from the self-induced dipoles, and the atomic partial charges and polarizabilities can be fitted simultaneously against ESP in a unified manner. The fitting with 1-ethyl-3-methylimidazolium (EMIM+) and nitrate (NO3-), a prototypical organic cation and inorganic anion, respectively, that can form ionic liquid, demonstrates that allowance of the self-induced dipoles gives much better fitness. Moreover, test on the total dipole of an EMIM+/NO3- ion pair shows that the agreement with the ab initio dipole is also much improved for the polarizable model, which highlights the importance of the polarization effects of ionic liquids.

PyRESP: A Program for Electrostatic Parameterizations of Additive and Induced Dipole Polarizable Force Fields.

Molecular modeling at the atomic level has been applied in a wide range of biological systems. The widely adopted additive force fields typically use fixed atom-centered partial charges to model electrostatic interactions. However, the additive force fields cannot accurately model polarization effects, leading to unrealistic simulations in polarization-sensitive processes. Numerous efforts have been invested in developing induced dipole-based polarizable force fields. Whether additive atomic charge models or polarizable induced dipole models are used, proper parameterization of the electrostatic term plays a key role in the force field developments. In this work, we present a Python program called PyRESP for performing atomic multipole parameterizations by reproducing ab initio electrostatic potential (ESP) around molecules. PyRESP provides parameterization schemes for several electrostatic models, including the RESP model with atomic charges for the additive force fields and the RESP-ind and RESP-perm models with additional induced and permanent dipole moments for the polarizable force fields. PyRESP is a flexible and user-friendly program that can accommodate various needs during force field parameterizations for molecular modeling of any organic molecules.

How can fluorine directly and indirectly affect the hydrogen bonding in molecular systems? – A case study for monofluoroanilines

Hydrogen bonds (HBs) directly engaging fluorine has been extensively studied, but the indirect effect of fluorine on adjacent donors and acceptors is poorly understood and still difficult to predict. The indirect and direct effect of the fluorination of aniline on HB patterns observed in monofluoroanilines was studied via experimental (vibrational spectroscopy and crystal structure analysis) and theoretical (ab initio molecular dynamics and electrostatic surface potential) methods. It was found that a fluorine substituent decreases the strength and frequency of N–H⋯N HBs and, at the same time, increases the acidity of CH protons, enhancing the competitiveness of weaker interactions. Additionally, the position of fluorine in the aromatic ring strongly affects the C–F bond length, and a direct intramolecular N–H⋯F HB causes an increase in the N–H bond stability. We also provide a methodology to identify and separate individual HBs concerning the type of donor or acceptor from the ab initio molecular dynamics trajectories.

Improved general-purpose five-point model for water: TIP5P/2018.

A new five point potential for liquid water, TIP5P/2018, is presented along with the techniques used to derive its charges from ab initio per-molecule electrostatic potentials in the liquid phase using the split charge equilibration of Nistor et al. [J. Chem. Phys. 125, 094108 (2006)]. By taking the density and diffusion dependence on temperature as target properties, significant improvements to the behavior of isothermal compressibility were achieved along with improvements to other thermodynamic and rotational properties. While exhibiting a dipole moment close to ab initio values, TIP5P/2018 suffers from a too small quadrupole moment due to the charge assignment procedure and results in an overestimation of the dielectric constant.

Prelude to molecular dynamics: Topography‐driven gaussian charge models

AbstractA new strategy to develop Gaussian charge models (GCMs) for molecules like ammonia, water, ethene, hydrogen sulfide, formaldehyde and benzene is presented. These molecular models comprising of positive point charges and negative Gaussian charge distributions (GCDs), which represent nuclei and continuous electron charge distribution, are found to correctly represent the ab initio Molecular Electrostatic Potential (MESP) and reproduce its essential topographical features of corresponding molecules. The models use optimized parameters: positive charges at nuclei, negative charges on GCDs, Gaussian exponent and centers. The Potential Energy Surface (PES) of water dimer has been explored using water GCMs. A good agreement has been found between PES obtained using GCMs and wave function. The Gaussian models correctly predict structure of benzene‐water complex. It is thus recommended to use GCMs for molecular dynamic simulations.

Efficient first principles simulation of electron scattering factors for transmission electron microscopy

Electron microscopy is a powerful tool for studying the properties of materials down to their atomic structure. In many cases, the quantitative interpretation of images requires simulations based on atomistic structure models. These typically use the independent atom approximation that neglects bonding effects, which may, however, be measurable and of physical interest. Since all electrons and the nuclear cores contribute to the scattering potential, simulations that go beyond this approximation have relied on computationally highly demanding all-electron calculations. Here, we describe a new method to generate ab initio electrostatic potentials when describing the core electrons by projector functions. Combined with an interface to quantitative image simulations, this implementation enables an easy and fast means to model electron scattering. We compare simulated transmission electron microscopy images and diffraction patterns to experimental data, showing an accuracy equivalent to earlier all-electron calculations at a much lower computational cost.

Multipole models of sulphur for accurate anisotropic electrostatic interactions within force fields

Nowadays, as computing has become much more available, a fresh momentum has been observed in the field of re-visioning and re-parameterizing the usual tools, as well as estimating for the incorporation of new qualitative capabilities, aimed at making more accurate and reliable predictions in drug discovery processes. Inspired by the success of modelling the electrostatic part of the halogen bonding (XB) by means of the distributed multipole expansion, a study is presented which attempts to extend this approach to a tougher case of σ-hole interaction: sulphur-based chalcogen bonding. To that end, 11 anisotropic models have been derived and tested for their performance in the reproduction of reference ab initio molecular electrostatic potential. A careful examination resulted in three models which have been selected for further examination as a part of the molecular mechanics force field (GAFF). The combined force field was used to estimate inter- and intra-molecular interactions for the molecular systems, capable of differentiating the binding from the σ-hole and other directions. The anisotropic models proposed were generally able to correct the wrong predictions of the sulphur models based only on isotropic charges and, thus, are a promising direction for further development of the refined electrostatics force fields.

Minimal distributed charges: Multipolar quality at the cost of point charge electrostatics.

Most empirical force fields use atom-centered point charges (PCs) to represent the electrostatic potential (ESP) around molecules. While such PC models are computationally efficient, they are unable to capture anisotropic electronic features, such as σ holes or lone pairs. These features are better described using atomic multipole (MTP) moments, which significantly improve the quality of the resulting ESP. However, the improvement comes at the expense of a considerably increased computational complexity and cost for calculating the interaction energies and forces. In the present work, a novel minimal distributed charge model (MDCM) based on off-centered point charges is presented and the quality of the resulting ESP is compared to the performance of MTPs and atom-centered PC models for several test molecules. All three models are fitted using the same algorithm based on differential evolution, which is available as a Fortran90 program from the authors upon request. We show that the MDCM is capable of approximating the reference ab initio ESP with an accuracy as good as, or better than, MTPs without the need for computationally expensive higher order multipoles. Further it is demonstrated that the MDCM is numerically stable in molecular dynamics simulations and is able to reproduce electrostatic interaction energies and thermodynamic quantities with the same accuracy as MTPs at reduced computational cost.

A model with charges and polarizability for CS2 in an ionic liquid

The environment of a solute molecule in an ionic liquid is likely to have large fluctuating electrostatic fields, and so the electrostatic properties of such a solute including its charge distribution and its polarizability may make a difference to both its static and dynamic properties. We have developed a new model for the static electrostatic distribution in the CS2 molecule with 7 charged sites and anisotropic polarizability on the carbon site and isotropic polarizability on the sulfurs. We have investigated static and dynamic properties of the neat liquid and solutions of CS2 in an ionic liquid, [dmim][NTf2]. Left: ab initio electrostatic potential (volt) on the vdW×1.5 surface of CS2; middle: difference between 3-site model and an initio; right: difference between 7-site model and ab inito.

Development of a Simple Electron Transfer and Polarization Model and Its Application to Biological Systems.

Here we present a new method for point charge calculation which we call QET (charges by electron transfer). The intent of this work is to develop a method that can be useful for studying charge transfer in large biological systems. It is based on the intuitive framework of the QEQ method with the key difference being that the QET method tracks all pairwise electron transfers by augmenting the QEQ pseudoenergy function with a distance dependent cost function for each electron transfer. This approach solves the key limitation of the QEQ method which is its handling of formally charged groups. First, we parametrize the QET method by fitting to electrostatic potentials calculated using ab initio quantum mechanics on over 11,000 small molecules. On an external test set of over 2500 small molecules the QET method achieves a mean absolute error of 1.37 kcal/mol/electron when compared to the ab initio electrostatic potentials. Second, we examine the conformational dependence of the charges on over 2700 tripeptides. With the tripeptide data set, we show that the conformational effects account for approximately 0.4 kcal/mol/electron on the electrostatic potentials. Third, we test the QET method for its ability to reproduce the effects of polarization and electron transfer on 1000 water clusters. For the water clusters, we show that the QET method captures about 50% of the polarization and electron transfer effects. Finally, we examine the effects of electron transfer and polarizability on the electrostatic interaction between p38 and 94 small molecule ligands. When used in conjunction with the Generalized-Born continuum solvent model, polarization and electron transfer with the QET model lead to an average change of 17 kcal/mol on the calculated electrostatic component of ΔG.

A Toolkit to Fit Nonbonded Parameters from and for Condensed Phase Simulations.

The quality of atomistic simulations depends decisively on the accuracy of the underlying energy function (force field). Of particular importance for condensed-phase properties are nonbonded interactions, including the electrostatic and Lennard-Jones terms. Permanent atomic multipoles (MTPs) are an extension to common point-charge (PC) representations in atomistic simulations. MTPs are commonly determined from and fitted to an ab initio Electrostatic Potential (ESP), and Lennard-Jones (LJ) parameters are obtained from comparison of experimental and computed observables using molecular dynamics (MD) simulations. For this a set of thermodynamic observables such as density, heat of vaporization, and hydration free energy is chosen, to which the parametrization is fitted. The current work introduces a comprehensive computing environment (Fitting Wizard (FW)) for optimizing nonbonded interactions for atomistic force fields of different qualities. The FW supports fitting of standard PC-based force fields and more physically motivated multipolar (MTP) force fields. A broader study including 20 molecules ranging from N-methyl-acetamide and benzene to halogenated benzenes, phenols, anilines, and pyridines yields a root mean squared deviation for hydration free energies of 0.36 kcal/mol over a range of 8 kcal/mol. It is furthermore shown that PC-based force fields are not necessarily inferior compared to MTP parametrizations depending on the molecule considered.

Perspectives of Halogen Bonding Description in Scoring Functions and QSAR/QSPR: Substituent Effects in Aromatic Core.

Halogen bonding (XB) is a new promising interaction pattern in medicinal chemistry. It has predominantly electrostatic nature - high electrostatic potential anisotropy. However to fully unleash the potential of XB in rational drug design fast and robust empirical methods of XB description should be developed. Current approaches rely heavily on ab initio calculation for each molecule studied. Thus fast prediction of electrostatic parameters for description of XB for arbitrary organic molecules is of paramount importance to promptly establish QSAR/QSPR, virtual screening and molecular docking pipelines suitable for today's agile development requirements. The two most promising approaches to describe anisotropic electrostatic models - the extra point (EP) charge model and the multipole expansion (ME) model - were studied on their ability (1) to describe ab initio molecular electrostatic potential (MEP) and (2) to produce parameters that can be predicted for each molecule empirically rather than estimated via ab initio calculations. The reference ab initio MEP was calculated for a set of 730 substituted halobenzenes. Parameters for anisotropic electrostatics of both empirical models (EP and ME) studied were extracted from ab initio MEP. The FreeWilson and Hansch type QSPR models relating XB parameters with aromatic substituents were built and analyzed, providing the guidelines for further development.

An atomic charge model for graphene oxide for exploring its bioadhesive properties in explicit water.

Graphene Oxide (GO) has been shown to exhibit properties that are useful in applications such as biomedical imaging, biological sensors, and drug delivery. The binding properties of biomolecules at the surface of GO can provide insight into the potential biocompatibility of GO. Here we assess the intrinsic affinity of amino acids to GO by simulating their adsorption onto a GO surface. The simulation is done using Amber03 force-field molecular dynamics in explicit water. The emphasis is placed on developing an atomic charge model for GO. The adsorption energies are computed using atomic charges obtained from an ab initio electrostatic potential based method. The charges reported here are suitable for simulating peptide adsorption to GO.

FOHI-D: an iterative Hirshfeld procedure including atomic dipoles.

In this work, a new partitioning method based on the FOHI method (fractional occupation Hirshfeld-I method) will be discussed. The new FOHI-D method uses an iterative scheme in which both the atomic charge and atomic dipole are calculated self-consistently. In order to induce the dipole moment on the atom, an electric field is applied during the atomic SCF calculations. Based on two sets of molecules, the atomic charge and intrinsic atomic dipole moment of hydrogen and chlorine atoms are compared using the iterative Hirshfeld (HI) method, the iterative Stockholder atoms (ISA) method, the FOHI method, and the FOHI-D method. The results obtained are further analyzed as a function of the group electronegativity of Boyd et al. [J. Am. Chem. Soc. 110, 4182 (1988); Boyd et al., J. Am. Chem. Soc. 114, 1652 (1992)] and De Proft et al. [J. Phys. Chem. 97, 1826 (1993)]. The molecular electrostatic potential (ESP) based on the HI, ISA, FOHI, and FOHI-D charges is compared with the ab initio ESP. Finally, the effect of adding HI, ISA, FOHI, and FOHI-D atomic dipoles to the multipole expansion as a function of the precision of the ESP is analyzed.

Modeling Organochlorine Compounds and the σ-Hole Effect Using a Polarizable Multipole Force Field

The charge distribution of halogen atoms on organochlorine compounds can be highly anisotropic and even display a so-called σ-hole, which leads to strong halogen bonds with electron donors. In this paper, we have systematically investigated a series of chloromethanes with one to four chloro substituents using a polarizable multipole-based molecular mechanics model. The atomic multipoles accurately reproduced the ab initio electrostatic potential around chloromethanes, including CCl4, which has a prominent σ-hole on the Cl atom. The van der Waals parameters for Cl were fitted to the experimental density and heat of vaporization. The calculated hydration free energy, solvent reaction fields, and interaction energies of several homo- and heterodimer of chloromethanes are in good agreement with experimental and ab initio data. This study suggests that sophisticated electrostatic models, such as polarizable atomic multipoles, are needed for accurate description of electrostatics in organochlorine compounds and halogen bonds, although further improvement is necessary for better transferability.

Multipoles as Force Field Parameters - Accuracy and Redundancy

Simulation of proteins and other large biomolecules rely on a force field representation of the potential energy surface. Fixed charge force fields, like AMBER, CHARMM, OPLS, and GROMOS, are widely used, however, it is well known that they, due to their simplicity provide an inaccurate description of the electrostatic energy component.In this study, multipoles up to quadrupoles are fitted to reproduce an ab initio electrostatic potential. The accuracy gained by introducing higher order multipoles is significant. However, the inclusion of multipoles as electrostatic parameters is highly associated with additional redundancy among the parameters. In an attempt to resolve redundancy, a large fraction of less important multipoles were identified and eliminated, without affecting the accuracy of the electrostatic potential. Furthermore, it is concluded that the reduced set of chemically important multipoles is transferable to different geometries of the same molecule. This is a promising result with respect to force field development, which highly relies on the assumption of transferability.

Deriving Static Atomic Multipoles from the Electrostatic Potential

The description of molecular systems using multipolar electrostatics calls for automated methods to fit the necessary parameters. In this paper, we describe an open-source software package that allows fitting atomic multipoles (MTPs) from the ab initio electrostatic potential by adequate atom typing and judicious assignment of the local axis system. By enabling the simultaneous fit of several molecules and/or conformations, the package addresses issues of parameter transferability and lack of sampling for buried atoms. We illustrate the method by studying a series of small alcohol molecules, as well as various conformations of protonated butylamine.

Polarized Protein-Specific Charges from Atoms-in-Molecule Electron Density Partitioning

Atomic partial charges for use in traditional force fields for biomolecular simulation are often fit to the electrostatic potentials of small molecules and, hence, neglect large-scale electronic polarization. On the other hand, recent advances in atoms-in-molecule charge derivation schemes show promise for use in flexible force fields but are limited in size by the underlying quantum mechanical calculation of the electron density. Here, we implement the density derived electrostatic and chemical charges method in the linear-scaling density functional theory code ONETEP. Our implementation allows the straightforward derivation of partial atomic charges for systems comprising thousands of atoms, including entire proteins. We demonstrate that the derived charges are chemically intuitive, reproduce ab initio electrostatic potentials of proteins and are transferable between closely related systems. Simulated NMR data derived from molecular dynamics of three proteins using force fields based on the ONETEP charges are in good agreement with experiment.

Multipole-Based Force Fields from ab Initio Interaction Energies and the Need for Jointly Refitting All Intermolecular Parameters.

Distributed atomic multipole (MTP) moments promise significant improvements over point charges (PCs) in molecular force fields, as they (a) more realistically reproduce the ab initio electrostatic potential (ESP) and (b) allow to capture anisotropic atomic properties such as lone pairs, conjugated systems, and σ holes. The present work focuses on the question of whether multipolar electrostatics instead of PCs in standard force fields leads to quantitative improvements over point charges in reproducing intermolecular interactions. To this end, the interaction energies of two model systems, benzonitrile (BZN) and formamide (FAM) homodimers, are characterized over a wide range of dimer conformations. It is found that although with MTPs the monomer ab initio ESP can be captured better by about an order of magnitude compared to point charges (PCs), this does not directly translate into better describing ab initio interaction energies compared to PCs. Neither ESP-fitted MTPs nor refitted Lennard-Jones (LJ) parameters alone demonstrate a clear superiority of atomic MTPs. We show that only if both electrostatic and LJ parameters are jointly optimized in standard, nonpolarizable force fields, atomic are MTPs clearly beneficial for reproducing ab initio dimerization energies. After an exhaustive exponent scan, we find that for both BZN and FAM, atomic MTPs and a 9-6 LJ potential can reproduce ab initio interaction energies with ∼30% (RMSD 0.13 vs 0.18 kcal/mol) less error than point charges (PCs) and a 12-6 LJ potential. We also find that the improvement due to using MTPs with a 9-6 LJ potential is considerably more pronounced than with a 12-6 LJ potential (≈ 10%; RMSD 0.19 versus 0.21 kcal/mol).

Ab initio based large-scale screening of hypothetical MOFs for carbon capture application

ABSTRACTMetal organic frameworks (MOFs) are porous solids that are potential high performance carbon capture materials. We have mined a hypothetical MOF database for structures that have exceptional low-pressure CO2 adsorption properties. We have applied the REPEAT method to generate accurate atomic charges that regenerate the ab initio electrostatic potential. We show that large scale screening at high accuracy is feasible for thousands of structures. We identify promising synthesis targets, like a simple combination of chrysene linker and vanadium inorganic unit, and examine in detail structural features that make better performing MOFs from those that would not be synthesisable. We find that, although screening large numbers of hypothetical structures is necessary to provide experimental targets, there are limitations to the suggestion of using the this database directly for synthesis targets and propose improvements and constraints that should be incorporated into the design of further generations of such a building-block algorithm to reach the accuracy required for high-quality CO2 adsorption simulation.