Fast Atomic Charge Calculation for Implementation into a Polarizable Force Field and Application to an Ion Channel Protein

Polarization of atoms plays a substantial role in molecular interactions. Class I and II force fields mostly calculate with fixed atomic charges which can cause inadequate descriptions for highly charged molecules, for example, ion channels or metalloproteins. Changes in charge distributions can be included into molecular mechanics calculations by various methods. Here, we present a very fast computational quantum mechanical method, the Bond Polarization Theory (BPT). Atomic charges are obtained via a charge calculation method that depend on the 3D structure of the system in a similar way as atomic charges ofab initiocalculations. Different methods of population analysis and charge calculation methods and their dependence on the basis set were investigated. A refined parameterization yielded excellent correlation ofR=0.9967. The method was implemented in the force field COSMOS-NMR and applied to the histidine-tryptophan-complex of the transmembrane domain of the M2 protein channel of influenza A virus. Our calculations show that moderate changes of side chain torsion angleχ1and small variations ofχ2of Trp-41 are necessary to switch from the inactivated into the activated state; and a rough two-side jump model of His-37 is supported for proton gating in accordance with a flipping mechanism.

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Structure and bonding in square-planar chalcogen rings

Canadian Journal of Chemistry ◽

10.1139/v92-049 ◽

1992 ◽

Vol 70 (2) ◽

pp. 348-352 ◽

Cited By ~ 15

Author(s):

Leif J. Saethre ◽

Odd Gropen

Keyword(s):

Potential Model ◽

Population Analysis ◽

Atomic Charge ◽

Molecular Structures ◽

Basis Set ◽

Single Bond ◽

Bond Lengths ◽

Square Planar ◽

Structure And Bonding ◽

D Orbitals

The molecular structures of square-planar X42+, X4+, and X4 (X = S, Se, Te) have been calculated using the effective core potential model. For X42+ the agreement between experimental and calculated values is excellent provided that d orbitals are included in the basis set. For the hypothetical molecules X4+ and X4 the bond lengths are found to increase dramatically as one and, subsequently, two electrons are added to the systems. Extensive population analysis shows that this increase is almost exclusively due to loss of bonding in the π system, whereas the bonding in the σ system remains relatively unaltered. These results make it possible to predict covalent single bond radii for S, Se, and Te for which the influence of π repulsion is removed. From the calculated variation of bond lengths with atomic charge, bond lengths are predicted for a series of planar disulphide rings. Keywords: structure, bonding, chalcogen, theoretical, ECP.

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Mulliken-Dipole Population Analysis

10.26434/chemrxiv.12722072 ◽

2020 ◽

Author(s):

Daniel G Trabada ◽

Diego Soler-Polo ◽

Jesus I. Mendieta-Moreno ◽

José Ortega

Keyword(s):

Dipole Moment ◽

Good Description ◽

Dipole Moments ◽

Population Analysis ◽

Atomic Charge ◽

Atomistic Simulations ◽

Atomic Charges ◽

Mulliken Population ◽

Basic Hypothesis ◽

Bond Direction

Atomic charge is one of the most important concepts in Chemistry. Mulliken population analysis is historically the most important method to calculate atomic charges and is still widely used. One basic hypothesis of this method is the half-and-half partition of the overlap populations, Q(μ, <i>v</i>), into equal charges in orbitals μ and <i>v</i>. This partition preserves the monopole moment of the overlap density but, other than that, is arbitrary. In this work we derive a new population analysis (which we designate Mulliken-Dipole population analysis) based on the conservation of both the monopole moment and the dipole moment along the bond direction. Test calculations show that the Mulliken-Dipole atomic charges are in accord to the chemical intuition; also they are very different from the Mulliken ones, being quite similar to the Hirshfeld atomic charges. Mulliken-Dipole atomic charges are conceptually appealing and very easy to calculate. In a further step, we also show how this Mulliken-Dipole population analysis can be used to derive atomic charges for atomistic simulations that reproduce the total dipole moment of the molecule, yielding at the same time a good description of the local charges and dipole moments for the molecular fragments.<br>

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Mulliken-Dipole Population Analysis

10.26434/chemrxiv.12722072.v1 ◽

2020 ◽

Author(s):

Daniel G Trabada ◽

Diego Soler-Polo ◽

Jesus I. Mendieta-Moreno ◽

José Ortega

Keyword(s):

Dipole Moment ◽

Good Description ◽

Dipole Moments ◽

Population Analysis ◽

Atomic Charge ◽

Atomistic Simulations ◽

Atomic Charges ◽

Mulliken Population ◽

Basic Hypothesis ◽

Bond Direction

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Molecular Structural and Vibrational Spectroscopic Assignments of n5-(4-Methoxyphenyl)-3-(1-methylindol-3-yl)-isoxazole using DFT Theory Calculations

Asian Journal of Organic & Medicinal Chemistry ◽

10.14233/ajomc.2019.ajomc-p186 ◽

2019 ◽

Vol 4 (3) ◽

pp. 147-151

Author(s):

J. Jani Matilda ◽

T.F. Abbs Fen Reji

Keyword(s):

Molecular Orbital ◽

Density Functional ◽

Population Analysis ◽

Nbo Analysis ◽

Basis Set ◽

Atomic Charges ◽

Dft Methods ◽

Mulliken Population ◽

B3lyp Method ◽

Experimental Values

In an effort to evaluate and design fast, accurate density functional theory (DFT) methods for 5-(4- methoxyphenyl)-3-(1-methylindol-3yl)isoxazole compound was done using Gaussion’ 09 program package using B3LYP method with the 6-31G basis set, which has been successfully applied in order to derive the optimized geometry, bonding features, harmonic vibrational wave numbers, NBO analysis and Mulliken population analysis on atomic charges in the ground state. Optimized geometries of the molecule have been described and collate with the experimental values. The experimental atomic charges demonstrates adequate concurrence with the theoretical prediction from DFT. The theoretical spectra values have been interpreted and compared with the FT-IR spectra. The calculated highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy gaps also confirm that charge transfer takes place within the molecule.

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PROBING THE INTERPLAY BETWEEN MULTIPLICITY AND IONICITY OF THE CHEMICAL BOND

Journal of Theoretical and Computational Chemistry ◽

10.1142/s021963361100658x ◽

2011 ◽

Vol 10 (04) ◽

pp. 471-482 ◽

Cited By ~ 10

Author(s):

DARIUSZ SZCZEPANIK ◽

JANUSZ MROZEK

Keyword(s):

Chemical Bond ◽

Population Analysis ◽

Atomic Charge ◽

Numerical Results ◽

Basis Set ◽

Chemical Bonds ◽

Bond Multiplicity ◽

Bond Covalency ◽

Type Bond

A new bond multiplicity measure based on the Wiberg-type bond covalency index and the atomic charge from population analysis is presented. Heuristically derived formulas allow one to evaluate the character of the chemical bond, especially its ionicity degree. Numerical results at RHF/ROHF theory level demonstrate that full multiplicities of typical chemical bonds are close to formal orders and their basis set dependence is inconsiderable, especially for highly polarized chemical bonds.

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Hydration Free Energies of Organic Molecules in the FreeSolv Database Calculated with Polarized Atom In Molecules Atomic Charges and the GAFF Force Field.

10.26434/chemrxiv.6015611.v1 ◽

2018 ◽

Author(s):

Maximiliano Riquelme ◽

Alejandro Lara ◽

David L. Mobley ◽

Toon Vestraelen ◽

Adelio R Matamala ◽

...

Keyword(s):

Force Field ◽

Functional Groups ◽

Electrostatic Interactions ◽

Organic Molecules ◽

Force Fields ◽

Chemical Elements ◽

Atomic Charges ◽

Free Energies ◽

Molecular Systems ◽

Solvent Model

<div>Computer simulations of bio-molecular systems often use force fields, which are combinations of simple empirical atom-based functions to describe the molecular interactions. Even though polarizable force fields give a more detailed description of intermolecular interactions, nonpolarizable force fields, developed several decades ago, are often still preferred because of their reduced computation cost. Electrostatic interactions play a major role in bio-molecular systems and are therein described by atomic point charges.</div><div>In this work, we address the performance of different atomic charges to reproduce experimental hydration free energies in the FreeSolv database in combination with the GAFF force field. Atomic charges were calculated by two atoms-in-molecules approaches, Hirshfeld-I and Minimal Basis Iterative Stockholder (MBIS). To account for polarization effects, the charges were derived from the solute's electron density computed with an implicit solvent model and the energy required to polarize the solute was added to the free energy cycle. The calculated hydration free energies were analyzed with an error model, revealing systematic errors associated with specific functional groups or chemical elements. The best agreement with the experimental data is observed for the MBIS atomic charge method, including the solvent polarization, with a root mean square error of 2.0 kcal mol<sup>-1</sup> for the 613 organic molecules studied. The largest deviation was observed for phosphor-containing molecules and the molecules with amide, ester and amine functional groups.</div>

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SAMPL6 Octanol-Water Partition Coefficients from Alchemical Free Energy Calculations with MBIS Atomic Charges

10.26434/chemrxiv.9924806 ◽

2019 ◽

Author(s):

Maximiliano Riquelme ◽

Esteban Vöhringer-Martinez

Keyword(s):

Free Energy ◽

Electron Density ◽

Free Energy Calculations ◽

Basis Set ◽

Energetic Cost ◽

Atomic Charges ◽

Free Energies ◽

Energy Calculations ◽

Alchemical Free Energy ◽

Alchemical Free Energy Calculations

In molecular modeling the description of the interactions between molecules forms the basis for a correct prediction of macroscopic observables. Here, we derive atomic charges from the implicitly polarized electron density of eleven molecules in the SAMPL6 challenge using the Hirshfeld-I and Minimal Basis Set Iterative Stockholder(MBIS) partitioning method. These atomic charges combined with other parameters in the GAFF force field and different water/octanol models were then used in alchemical free energy calculations to obtain hydration and solvation free energies, which after correction for the polarization cost, result in the blind prediction of the partition coefficient. From the tested partitioning methods and water models the S-MBIS atomic charges with the TIP3P water model presented the smallest deviation from the experiment. Conformational dependence of the free energies and the energetic cost associated with the polarization of the electron density are discussed.

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S-Acylation of Proteins of Coronavirus and Influenza Virus: Conservation of Acylation Sites in Animal Viruses and DHHC Acyltransferases in Their Animal Reservoirs

Pathogens ◽

10.3390/pathogens10060669 ◽

2021 ◽

Vol 10 (6) ◽

pp. 669

Author(s):

Dina A. Abdulrahman ◽

Xiaorong Meng ◽

Michael Veit

Keyword(s):

Influenza Virus ◽

Amino Acid ◽

Ion Channels ◽

Substrate Specificity ◽

Influenza A ◽

3D Structure ◽

Viral Fitness ◽

Amino Acid Substitutions ◽

Essential Function ◽

Animal Reservoirs

Recent pandemics of zoonotic origin were caused by members of coronavirus (CoV) and influenza A (Flu A) viruses. Their glycoproteins (S in CoV, HA in Flu A) and ion channels (E in CoV, M2 in Flu A) are S-acylated. We show that viruses of all genera and from all hosts contain clusters of acylated cysteines in HA, S and E, consistent with the essential function of the modification. In contrast, some Flu viruses lost the acylated cysteine in M2 during evolution, suggesting that it does not affect viral fitness. Members of the DHHC family catalyze palmitoylation. Twenty-three DHHCs exist in humans, but the number varies between vertebrates. SARS-CoV-2 and Flu A proteins are acylated by an overlapping set of DHHCs in human cells. We show that these DHHC genes also exist in other virus hosts. Localization of amino acid substitutions in the 3D structure of DHHCs provided no evidence that their activity or substrate specificity is disturbed. We speculate that newly emerged CoVs or Flu viruses also depend on S-acylation for replication and will use the human DHHCs for that purpose. This feature makes these DHHCs attractive targets for pan-antiviral drugs.

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Sequence analysis, structure prediction of receptor proteins and In silico study of potential inhibitors for management of life threatening COVID-19

Letters in Drug Design & Discovery ◽

10.2174/1570180818666210804141613 ◽

2021 ◽

Vol 18 ◽

Author(s):

Hriday K. Basak ◽

Soumen Saha ◽

Joydeep Ghosh ◽

Uttam Paswan ◽

Sujoy Karmakar ◽

...

Keyword(s):

Binding Site ◽

Ursolic Acid ◽

Density Functional ◽

Actinomycin D ◽

3D Structure ◽

Natural Compounds ◽

Surface Glycoprotein ◽

Basis Set ◽

3D Structures ◽

Potential Inhibitors

Background: Treatment of the Covid-19 pandemic caused by the highly contagious and pathogenic SARS-CoV-2 is a global menace. Day by day this pandemic is getting worse. Doctors, Scientists and Researchers across the world are urgently scrambling for a cure for novel corona virus and continuously working at break neck speed to develop vaccine or drugs. But to date, there are no specific drugs or vaccine available in the market to cope up the virus. Objective: The present study helps us to elucidate 3D structures of SARS-CoV-2 proteins and also to identify best natural compounds as potential inhibitors against COVID-19. Methods: The 3D structures of the proteins were constructed using Modeller 9.16 modeling tool. Modelled proteins were validated with PROCHECK by Ramachandran plot analysis. In this study a small library of natural compounds (fifty compounds) was docked to the ACE2 binding site of the modelled surface glycoprotein of SARS-CoV-2 using Auto Dock Vina to repurpose these inhibitors for SARS-CoV-2. Conceptual density functional theory calculations of best eight compounds had been performed by Gaussian-09. Geometry optimizations for these molecules were done at M06-2X/ def2-TZVP level of theory. ADME parameters, pharmacokinetic properties and drug likeliness of the compounds were analyzed in the swissADME website. Results: In this study we analysed the sequences of surface glycoprotein, nucleocapsid phosphoprotein and envelope protein obtained from different parts of the globe. We have modelled all the different sequences of surface glycoprotein and envelop protein in order to derive 3D structure of a molecular target which is essential for the development of therapeutics. Different electronic properties of the inhibitors have been calculated using DFT through M06-2X functional with def2-TZVP basis set. Docking result at the hACE2 binding site of all modelled surface glycoproteins of SARS-CoV-2 showed that all the eight inhibitors (Actinomycin D, avellanin C, ichangin, kanglemycin A, obacunone, ursolic acid, ansamiotocin P-3 and isomitomycin A) studied here many folds better compared to hydroxychloroquine which has been found to be effective to treat patients suffering fromCOVID-19 pandemic. All the inhibitors meet most of criteria of drug likeness assessment. Conclusion: We will expect that eight compounds (Actinomycin D, avellanin C, ichangin, kanglemycin A, obacunone, ursolic acid, ansamiotocin P-3 and isomitomycin A) can be used as potential inhibitors against SARS-CoV-2.

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Using Atomic Charges to Model Molecular Polarization.

Physical Chemistry Chemical Physics ◽

10.1039/d1cp03542h ◽

2022 ◽

Author(s):

Frank Jensen

Keyword(s):

Force Fields ◽

Atomic Charge ◽

Electric Polarization ◽

Special Focus ◽

Atomic Charges ◽

Electrical Polarization

We review different models for introducing electrical polarization in force fields, with special focus on methods where polarization is modelled at the atomic charge level. While electric polarization has been...

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