Field-SEA: A Model for Computing the Solvation Free Energies of Nonpolar, Polar, and Charged Solutes in Water

Previous work describes a computational solvation model called semi-explicit assembly (SEA). The SEA water model computes the free energies of solvation of nonpolar and polar solutes in water with good efficiency and accuracy. However, SEA gives systematic errors in the solvation free energies of ions and charged solutes. Here, we describe field-SEA, an improved treatment that gives accurate solvation free energies of charged solutes, including monatomic and polyatomic ions and model dipeptides, as well as nonpolar and polar molecules. Field-SEA is computationally inexpensive for a given solute because explicit-solvent model simulations are relegated to a precomputation step and because it represents solvating waters in terms of a solute’s free-energy field. In essence, field-SEA approximates the physics of explicit-model simulations within a computationally efficient framework. A key finding is that an atom’s solvation shell inherits characteristics of a neighboring atom, especially strongly charged neighbors. Field-SEA may be useful where there is a need for solvation free-energy computations that are faster than explicit-solvent simulations and more accurate than traditional implicit-solvent simulations for a wide range of solutes.

[1]  Asim Okur,et al.  Improved Efficiency of Replica Exchange Simulations through Use of a Hybrid Explicit/Implicit Solvation Model. , 2006, Journal of chemical theory and computation.

[2]  Arieh Warshel,et al.  A surface constrained all‐atom solvent model for effective simulations of polar solutions , 1989 .

[3]  C. Tanford,et al.  The solubility of amino acids and two glycine peptides in aqueous ethanol and dioxane solutions. Establishment of a hydrophobicity scale. , 1971, The Journal of biological chemistry.

[4]  H. Berendsen,et al.  A LEAP-FROG ALGORITHM FOR STOCHASTIC DYNAMICS , 1988 .

[5]  Guanhua Hou,et al.  An implicit solvent model for SCC-DFTB with Charge-Dependent Radii. , 2010, Journal of chemical theory and computation.

[6]  M. Parrinello,et al.  Polymorphic transitions in single crystals: A new molecular dynamics method , 1981 .

[7]  Junmei Wang,et al.  Development and testing of a general amber force field , 2004, J. Comput. Chem..

[8]  David L Mobley,et al.  Charge asymmetries in hydration of polar solutes. , 2008, The journal of physical chemistry. B.

[9]  H. Scheraga,et al.  Accessible surface areas as a measure of the thermodynamic parameters of hydration of peptides. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Charles W. Kehoe,et al.  Testing the semi-explicit assembly solvation model in the SAMPL3 community blind test , 2012, Journal of Computer-Aided Molecular Design.

[11]  Stephen H. White,et al.  Experimentally determined hydrophobicity scale for proteins at membrane interfaces , 1996, Nature Structural Biology.

[12]  Gerrit Groenhof,et al.  GROMACS: Fast, flexible, and free , 2005, J. Comput. Chem..

[13]  David A. Case,et al.  Soft‐core potentials in thermodynamic integration: Comparing one‐ and two‐step transformations , 2011, J. Comput. Chem..

[14]  Pengyu Y. Ren,et al.  Polarizable Atomic Multipole Water Model for Molecular Mechanics Simulation , 2003 .

[15]  David L Mobley,et al.  Treating entropy and conformational changes in implicit solvent simulations of small molecules. , 2008, The journal of physical chemistry. B.

[16]  T. Straatsma,et al.  Multiconfiguration thermodynamic integration , 1991 .

[17]  P. Kollman,et al.  Solvation Model Based on Weighted Solvent Accessible Surface Area , 2001 .

[18]  B. Honig,et al.  Classical electrostatics in biology and chemistry. , 1995, Science.

[19]  Michael R. Shirts,et al.  Comparison of efficiency and bias of free energies computed by exponential averaging, the Bennett acceptance ratio, and thermodynamic integration. , 2005, The Journal of chemical physics.

[20]  Matthew P Jacobson,et al.  Surfaces affect ion pairing. , 2005, The journal of physical chemistry. B.

[21]  Mark A Olson,et al.  An efficient hybrid explicit/implicit solvent method for biomolecular simulations , 2004, J. Comput. Chem..

[22]  C. Cramer,et al.  An SCF Solvation Model for the Hydrophobic Effect and Absolute Free Energies of Aqueous Solvation , 1992, Science.

[23]  W. C. Still,et al.  Semianalytical treatment of solvation for molecular mechanics and dynamics , 1990 .

[24]  A. Pohorille,et al.  An information theory model of hydrophobic interactions. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[25]  T. Darden,et al.  A smooth particle mesh Ewald method , 1995 .

[26]  B. Lee,et al.  The interpretation of protein structures: estimation of static accessibility. , 1971, Journal of molecular biology.

[27]  J. Guthrie,et al.  A blind challenge for computational solvation free energies: introduction and overview. , 2009, The journal of physical chemistry. B.

[28]  Guo-Wei Wei,et al.  Parameterization of a geometric flow implicit solvation model , 2013, J. Comput. Chem..

[29]  D. van der Spoel,et al.  GROMACS: A message-passing parallel molecular dynamics implementation , 1995 .

[30]  Ehud Y Isacoff,et al.  How does voltage open an ion channel? , 2006, Annual review of cell and developmental biology.

[31]  Berk Hess,et al.  LINCS: A linear constraint solver for molecular simulations , 1997, J. Comput. Chem..

[32]  M. Karplus,et al.  Effective energy function for proteins in solution , 1999, Proteins.

[33]  V. Hornak,et al.  Investigation of Salt Bridge Stability in a Generalized Born Solvent Model. , 2006, Journal of chemical theory and computation.

[34]  K. Sharp,et al.  Accurate Calculation of Hydration Free Energies Using Macroscopic Solvent Models , 1994 .

[35]  Charles W. Kehoe,et al.  Modeling aqueous solvation with semi-explicit assembly , 2011, Proceedings of the National Academy of Sciences.

[36]  A. Warshel,et al.  Calculations of Hydration Entropies of Hydrophobic, Polar, and Ionic Solutes in the Framework of the Langevin Dipoles Solvation Model , 1999 .

[37]  Toby W Allen,et al.  Potential of mean force and pKa profile calculation for a lipid membrane-exposed arginine side chain. , 2008, The journal of physical chemistry. B.

[38]  Jorge Nocedal,et al.  On the limited memory BFGS method for large scale optimization , 1989, Math. Program..

[39]  Alessandra Villa,et al.  Calculation of the free energy of solvation for neutral analogs of amino acid side chains , 2002, J. Comput. Chem..

[40]  Carsten Kutzner,et al.  GROMACS 4:  Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation. , 2008, Journal of chemical theory and computation.

[41]  Robert D Boyer,et al.  Fast estimation of solvation free energies for diverse chemical species. , 2012, The journal of physical chemistry. B.

[42]  C. Cramer,et al.  Implicit Solvation Models: Equilibria, Structure, Spectra, and Dynamics. , 1999, Chemical reviews.

[43]  J. Åqvist,et al.  Ion-water interaction potentials derived from free energy perturbation simulations , 1990 .

[44]  Andrew T. Fenley,et al.  Charge hydration asymmetry: the basic principle and how to use it to test and improve water models. , 2012, The journal of physical chemistry. B.

[45]  A. Mark,et al.  Coarse grained model for semiquantitative lipid simulations , 2004 .

[46]  Ken A Dill,et al.  Physical Modeling of Aqueous Solvation , 2011, Journal of statistical physics.

[47]  T. Cheatham,et al.  Determination of Alkali and Halide Monovalent Ion Parameters for Use in Explicitly Solvated Biomolecular Simulations , 2008, The journal of physical chemistry. B.

[48]  Benoît Roux,et al.  Generalized solvent boundary potential for computer simulations , 1999 .

[49]  A. D. McLachlan,et al.  Solvation energy in protein folding and binding , 1986, Nature.

[50]  Michael R. Shirts,et al.  Extremely precise free energy calculations of amino acid side chain analogs: Comparison of common molecular mechanics force fields for proteins , 2003 .

[51]  Charles W. Kehoe,et al.  Oil/water transfer is partly driven by molecular shape, not just size. , 2010, Journal of the American Chemical Society.

[52]  Traian Sulea,et al.  Restoring charge asymmetry in continuum electrostatics calculations of hydration free energies. , 2009, The journal of physical chemistry. B.

[53]  T. Ghosh,et al.  Size dependent ion hydration, its asymmetry, and convergence to macroscopic behavior. , 2004, The Journal of chemical physics.

[54]  J A McCammon,et al.  Coupling nonpolar and polar solvation free energies in implicit solvent models. , 2006, The Journal of chemical physics.

[55]  P M Cullis,et al.  Affinities of amino acid side chains for solvent water. , 1981, Biochemistry.

[56]  David A. Case,et al.  Effective Born radii in the generalized Born approximation: The importance of being perfect , 2002, J. Comput. Chem..

[57]  Irwin D Kuntz,et al.  Estimation of Absolute Free Energies of Hydration Using Continuum Methods: Accuracy of Partial Charge Models and Optimization of Nonpolar Contributions , 2022 .

[58]  David L Mobley,et al.  Accurate and efficient corrections for missing dispersion interactions in molecular simulations. , 2007, The journal of physical chemistry. B.

[59]  Ray Luo,et al.  Accelerated Poisson–Boltzmann calculations for static and dynamic systems , 2002, J. Comput. Chem..

[60]  H. Berendsen,et al.  Molecular dynamics with coupling to an external bath , 1984 .

[61]  S. Futaki,et al.  Methodological and cellular aspects that govern the internalization mechanisms of arginine-rich cell-penetrating peptides. , 2008, Advanced drug delivery reviews.

[62]  D. Beglov,et al.  Finite representation of an infinite bulk system: Solvent boundary potential for computer simulations , 1994 .

[63]  D. Case,et al.  Modification of the Generalized Born Model Suitable for Macromolecules , 2000 .

[64]  C. Brooks,et al.  Recent advances in the development and application of implicit solvent models in biomolecule simulations. , 2004, Current opinion in structural biology.

[65]  Nathan A. Baker,et al.  Electrostatics of nanosystems: Application to microtubules and the ribosome , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[66]  David L Mobley,et al.  Comparison of charge models for fixed-charge force fields: small-molecule hydration free energies in explicit solvent. , 2007, The journal of physical chemistry. B.

[67]  The effect of interactions involving ionizable residues flanking membrane-inserted hydrophobic helices upon helix-helix interaction. , 2003, Biochemistry.

[68]  W. L. Jorgensen,et al.  Comparison of simple potential functions for simulating liquid water , 1983 .

[69]  Kenneth S. Pitzer,et al.  The Free Energy of Hydration of Gaseous Ions, and the Absolute Potential of the Normal Calomel Electrode , 1939 .

[70]  B. Roux,et al.  Implicit solvent models. , 1999, Biophysical chemistry.

[71]  Mika A. Kastenholz,et al.  Computation of methodology-independent ionic solvation free energies from molecular simulations. I. The electrostatic potential in molecular liquids. , 2006, The Journal of chemical physics.

[72]  Nathan A. Baker,et al.  Assessing implicit models for nonpolar mean solvation forces: the importance of dispersion and volume terms. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[73]  J. Mccammon,et al.  Ewald artifacts in computer simulations of ionic solvation and ion–ion interaction: A continuum electrostatics study , 1999 .

[74]  G. Hummer,et al.  HYDROPHOBIC FORCE FIELD AS A MOLECULAR ALTERNATIVE TO SURFACE-AREA MODELS , 1999 .

[75]  B. Roux,et al.  Solvation Free Energy of Polar and Nonpolar Molecules in Water: An Extended Interaction Site Integral Equation Theory in Three Dimensions , 2000 .

[76]  A. Mark,et al.  Avoiding singularities and numerical instabilities in free energy calculations based on molecular simulations , 1994 .

[77]  T. Creamer,et al.  Solvation energies of amino acid side chains and backbone in a family of host-guest pentapeptides. , 1996, Biochemistry.

[78]  David L Mobley,et al.  Small molecule hydration free energies in explicit solvent: An extensive test of fixed-charge atomistic simulations. , 2009, Journal of chemical theory and computation.