Protein C-GeM: A Coarse-Grained Electron Model for Fast and Accurate Protein Electrostatics Prediction

The electrostatic potential (ESP) is a powerful property for understanding and predicting electrostatic charge distributions that drive interactions between molecules. In this study, we compare various charge partitioning schemes including fitted charges, density-based quantum mechanical (QM) partitioning schemes, charge equilibration methods, and our recently introduced coarse-grained electron model, C-GeM, to describe the ESP for protein systems. When benchmarked against high quality density functional theory calculations of the ESP for tripeptides and the crambin protein, we find that the C-GeM model is of comparable accuracy to ab initio charge partitioning methods, but with orders of magnitude improvement in computational efficiency since it does not require either the electron density or the electrostatic potential as input.

[1]  R. Wheatley,et al.  Atomic charge densities generated using an iterative stockholder procedure. , 2009, The Journal of chemical physics.

[2]  P. Kollman,et al.  An approach to computing electrostatic charges for molecules , 1984 .

[3]  P. Ayers,et al.  The conformational sensitivity of iterative stockholder partitioning schemes , 2012 .

[4]  Lixing Han,et al.  Implementing the Nelder-Mead simplex algorithm with adaptive parameters , 2010, Computational Optimization and Applications.

[5]  Margaret E. Johnson,et al.  Current status of the AMOEBA polarizable force field. , 2010, The journal of physical chemistry. B.

[6]  I. Leven,et al.  C-GeM: Coarse-Grained Electron Model for Predicting the Electrostatic Potential in Molecules. , 2019, The journal of physical chemistry letters.

[7]  Anmol Kumar,et al.  FFParam: Standalone package for CHARMM additive and Drude polarizable force field parametrization of small molecules , 2019, J. Comput. Chem..

[8]  Tom L. Blundell,et al.  New protein fold revealed by a 2.3-Å resolution crystal structure of nerve growth factor , 1991, Nature.

[9]  V. V. Speybroeck,et al.  The Monomer Electron Density Force Field (MEDFF): A Physically Inspired Model for Noncovalent Interactions. , 2017, Journal of chemical theory and computation.

[10]  Viki Kumar Prasad,et al.  PEPCONF, a diverse data set of peptide conformational energies , 2019, Scientific Data.

[11]  A. V. Duin,et al.  ReaxFF: A Reactive Force Field for Hydrocarbons , 2001 .

[12]  Steve Plimpton,et al.  Fast parallel algorithms for short-range molecular dynamics , 1993 .

[13]  P. Ayers,et al.  How pervasive is the Hirshfeld partitioning? , 2015, The Journal of chemical physics.

[14]  William A Goddard,et al.  Polarizable charge equilibration model for predicting accurate electrostatic interactions in molecules and solids. , 2017, The Journal of chemical physics.

[15]  John R. Kitchin,et al.  Neural network and ReaxFF comparison for Au properties , 2016 .

[16]  Sandeep Patel,et al.  Origin and control of superlinear polarizability scaling in chemical potential equalization methods. , 2008, The Journal of chemical physics.

[17]  P. Ayers,et al.  Minimal Basis Iterative Stockholder: Atoms in Molecules for Force-Field Development. , 2016, Journal of chemical theory and computation.

[18]  D Fincham,et al.  Shell model simulations by adiabatic dynamics , 1993 .

[19]  Radka Svobodová Vareková,et al.  Rapid Calculation of Accurate Atomic Charges for Proteins via the Electronegativity Equalization Method , 2013, J. Chem. Inf. Model..

[20]  M. Verdonk,et al.  Practical High-Quality Electrostatic Potential Surfaces for Drug Discovery Using a Graph-Convolutional Deep Neural Network. , 2019, Journal of medicinal chemistry.

[21]  C Z Wang,et al.  Molecule intrinsic minimal basis sets. I. Exact resolution of ab initio optimized molecular orbitals in terms of deformed atomic minimal-basis orbitals. , 2004, The Journal of chemical physics.

[22]  Victor Guallar,et al.  Importance of accurate charges in molecular docking: Quantum mechanical/molecular mechanical (QM/MM) approach , 2005, J. Comput. Chem..

[23]  J M Blaney,et al.  Electrostatic potential molecular surfaces. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[24]  David S Sholl,et al.  Chemically Meaningful Atomic Charges That Reproduce the Electrostatic Potential in Periodic and Nonperiodic Materials. , 2010, Journal of chemical theory and computation.

[25]  T Verstraelen,et al.  Hirshfeld-E Partitioning: AIM Charges with an Improved Trade-off between Robustness and Accurate Electrostatics. , 2013, Journal of chemical theory and computation.

[26]  Ross C. Walker,et al.  An overview of the Amber biomolecular simulation package , 2013 .

[27]  Jacopo Tomasi,et al.  The electrostatic molecular potential as a tool for the interpretation of molecular properties , 1973 .

[28]  J. Richardson,et al.  Asparagine and glutamine: using hydrogen atom contacts in the choice of side-chain amide orientation. , 1999, Journal of molecular biology.

[29]  F. Weinhold,et al.  Natural population analysis , 1985 .

[30]  P. Kollman,et al.  Automatic atom type and bond type perception in molecular mechanical calculations. , 2006, Journal of molecular graphics & modelling.

[31]  P. Ayers,et al.  An explicit approach to conceptual density functional theory descriptors of arbitrary order , 2016 .

[32]  Nathan A. Baker,et al.  PDB2PQR: an automated pipeline for the setup of Poisson-Boltzmann electrostatics calculations , 2004, Nucleic Acids Res..

[33]  Deriving the Hirshfeld partitioning using distance metrics. , 2014, The Journal of chemical physics.

[34]  Christopher I. Bayly,et al.  Fast, efficient generation of high‐quality atomic charges. AM1‐BCC model: II. Parameterization and validation , 2002, J. Comput. Chem..

[35]  Alán Aspuru-Guzik,et al.  Advances in molecular quantum chemistry contained in the Q-Chem 4 program package , 2014, Molecular Physics.

[36]  Jiahui Chen,et al.  Improvements to the APBS biomolecular solvation software suite , 2017, Protein science : a publication of the Protein Society.

[37]  Peter Politzer,et al.  The electrostatic potential: an overview , 2011 .

[38]  Wilfried J. Mortier,et al.  Electronegativity-equalization method for the calculation of atomic charges in molecules , 1986 .

[39]  Richard F. W. Bader.  A quantum theory of molecular structure and its applications , 1991 .

[40]  Yizeng Liang,et al.  A modified electronegativity equalization method for fast and accurate calculation of atomic charges in large biological molecules. , 2009, Physical chemistry chemical physics : PCCP.

[41]  Ananth Grama,et al.  Parallel reactive molecular dynamics: Numerical methods and algorithmic techniques , 2012, Parallel Comput..

[42]  Minsik Cho,et al.  The Atomic Partial Charges Arboretum: Trying to See the Forest for the Trees , 2020, Chemphyschem : a European journal of chemical physics and physical chemistry.

[43]  R. Parr,et al.  Information theory, atoms in molecules, and molecular similarity. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[44]  Narbe Mardirossian,et al.  ωB97X-V: a 10-parameter, range-separated hybrid, generalized gradient approximation density functional with nonlocal correlation, designed by a survival-of-the-fittest strategy. , 2014, Physical chemistry chemical physics : PCCP.

[45]  M. Teeter,et al.  Water structure of a hydrophobic protein at atomic resolution: Pentagon rings of water molecules in crystals of crambin. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[46]  C. Breneman,et al.  Determining atom‐centered monopoles from molecular electrostatic potentials. The need for high sampling density in formamide conformational analysis , 1990 .

[47]  Vincenzo Barone,et al.  Exploring the conformational and reactive dynamics of biomolecules in solution using an extended version of the glycine reactive force field. , 2013, Physical chemistry chemical physics : PCCP.

[48]  M. Head‐Gordon,et al.  Benchmarking the Performance of the ReaxFF Reactive Force Field on Hydrogen Combustion Systems. , 2020, The journal of physical chemistry. A.

[49]  Robert S. Mulliken,et al.  Electronic Population Analysis on LCAO‐MO Molecular Wave Functions. IV. Bonding and Antibonding in LCAO and Valence‐Bond Theories , 1955 .

[50]  Radka Svobodová Vareková,et al.  High-quality and universal empirical atomic charges for chemoinformatics applications , 2015, Journal of Cheminformatics.

[51]  Beatriz Cordero,et al.  Covalent radii revisited. , 2008, Dalton transactions.

[52]  Johann Gasteiger,et al.  Electronegativity equalization: application and parametrization , 1985 .

[53]  Toon Verstraelen,et al.  IOData: A python library for reading, writing, and converting computational chemistry file formats and generating input files , 2020, J. Comput. Chem..

[54]  P. Ayers,et al.  Information-Theoretic Approaches to Atoms-in-Molecules: Hirshfeld Family of Partitioning Schemes. , 2017, The journal of physical chemistry. A.

[55]  Gerald Knizia,et al.  Intrinsic Atomic Orbitals: An Unbiased Bridge between Quantum Theory and Chemical Concepts. , 2013, Journal of chemical theory and computation.

[56]  De-Li Chen,et al.  Atomic charges derived from electrostatic potentials for molecular and periodic systems. , 2010, The journal of physical chemistry. A.

[57]  Patrick Bultinck,et al.  Critical analysis and extension of the Hirshfeld atoms in molecules. , 2007, The Journal of chemical physics.