Implementation and testing of stable, fast implicit solvation in molecular dynamics using the smooth‐permittivity finite difference Poisson–Boltzmann method

A fast stable finite difference Poisson–Boltzmann (FDPB) model for implicit solvation in molecular dynamics simulations was developed using the smooth permittivity FDPB method implemented in the OpenEye ZAP libraries. This was interfaced with two widely used molecular dynamics packages, AMBER and CHARMM. Using the CHARMM‐ZAP software combination, the implicit solvent model was tested on eight proteins differing in size, structure, and cofactors: calmodulin, horseradish peroxidase (with and without substrate analogue bound), lipid carrier protein, flavodoxin, ubiquitin, cytochrome c, and a de novo designed 3‐helix bundle. The stability and accuracy of the implicit solvent simulations was assessed by examining root‐mean‐squared deviations from crystal structure. This measure was compared with that of a standard explicit water solvent model. In addition we compared experimental and calculated NMR order parameters to obtain a residue level assessment of the accuracy of MD‐ZAP for simulating dynamic quantities. Overall, the agreement of the implicit solvent model with experiment was as good as that of explicit water simulations. The implicit solvent method was up to eight times faster than the explicit water simulations, and approximately four times slower than a vacuum simulation (i.e., with no solvent treatment). © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 2049–2064, 2004

[1]  Ronald M. Levy,et al.  AGBNP: An analytic implicit solvent model suitable for molecular dynamics simulations and high‐resolution modeling , 2004, J. Comput. Chem..

[2]  Charles L. Brooks,et al.  Performance comparison of generalized born and Poisson methods in the calculation of electrostatic solvation energies for protein structures , 2004, J. Comput. Chem..

[3]  Michael Feig,et al.  Implicit solvation based on generalized Born theory in different dielectric environments. , 2004, The Journal of chemical physics.

[4]  Ray Luo,et al.  A Poisson–Boltzmann dynamics method with nonperiodic boundary condition , 2003 .

[5]  K. Sharp,et al.  Solvent dependent and independent motions of CO-horseradish peroxidase examined by infrared spectroscopy and molecular dynamics calculations. , 2003, Biophysical chemistry.

[6]  Sergio A Hassan,et al.  Molecular dynamics simulations of peptides and proteins with a continuum electrostatic model based on screened Coulomb potentials , 2003, Proteins.

[7]  Valerie Daggett,et al.  The complete folding pathway of a protein from nanoseconds to microseconds , 2003, Nature.

[8]  Dynamics and entropy of a calmodulin-peptide complex studied by NMR and molecular dynamics. , 2003, Biochemistry.

[9]  Temperature dependence of the internal dynamics of a calmodulin-peptide complex. , 2002, Biochemistry.

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

[11]  A. Wand,et al.  Structure of a de novo designed protein model of radical enzymes. , 2002, Journal of the American Chemical Society.

[12]  C. Brooks,et al.  Novel generalized Born methods , 2002 .

[13]  K. Sharp,et al.  Optical Spectra of Fe(II) Cytochrome c Interpreted Using Molecular Dynamics Simulations and Quantum Mechanical Calculations , 2002 .

[14]  A. Wand,et al.  Dissection of the pathway of molecular recognition by calmodulin. , 2002, Biochemistry.

[15]  Main chain and side chain dynamics of oxidized flavodoxin from Cyanobacterium anabaena. , 2001, Biochemistry.

[16]  T. Simonson,et al.  Protein molecular dynamics with the generalized born/ACE solvent model , 2001, Proteins.

[17]  David A. Case,et al.  Calculations of the Absolute Free Energies of Binding between RNA and Metal Ions Using Molecular Dynamics Simulations and Continuum Electrostatics , 2001 .

[18]  Andrew L. Lee,et al.  Microscopic origins of entropy, heat capacity and the glass transition in proteins , 2001, Nature.

[19]  J. Andrew Grant,et al.  A smooth permittivity function for Poisson–Boltzmann solvation methods , 2001, J. Comput. Chem..

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

[21]  D. Case,et al.  Molecular Dynamics Simulations of Nucleic Acids with a Generalized Born Solvation Model , 2000 .

[22]  M. Gilson,et al.  Comparison of generalized born and poisson models: Energetics and dynamics of HIV protease , 2000, J. Comput. Chem..

[23]  D. Case,et al.  Generalized born models of macromolecular solvation effects. , 2000, Annual review of physical chemistry.

[24]  Andrew L. Lee,et al.  Redistribution and loss of side chain entropy upon formation of a calmodulin–peptide complex , 2000, Nature Structural Biology.

[25]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[26]  B. Dominy,et al.  Development of a generalized Born model parameterization for proteins and nucleic acids , 1999 .

[27]  Comparison of 2H and 13C NMR Relaxation Techniques for the Study of Protein Methyl Group Dynamics in Solution , 1999 .

[28]  Bhyravabhotla Jayaram,et al.  Solvation Free Energy of Biomacromolecules: Parameters for a Modified Generalized Born Model Consistent with the AMBER Force Field , 1998 .

[29]  P. Kollman,et al.  Pathways to a protein folding intermediate observed in a 1-microsecond simulation in aqueous solution. , 1998, Science.

[30]  D. Beveridge,et al.  A MODIFICATION OF THE GENERALIZED BORN THEORY FOR IMPROVED ESTIMATES OF SOLVATION ENERGIES AND PK SHIFTS , 1998 .

[31]  K. Constantine,et al.  Backbone and side chain dynamics of uncomplexed human adipocyte and muscle fatty acid-binding proteins. , 1998, Biochemistry.

[32]  W. Im,et al.  Continuum solvation model: Computation of electrostatic forces from numerical solutions to the Poisson-Boltzmann equation , 1998 .

[33]  Bernard R. Brooks,et al.  Molecular Dynamics of Staphylococcal Nuclease: Comparison of Simulation with 15N and 13C NMR Relaxation Data , 1998 .

[34]  D. J. Schuller,et al.  Structural interactions between horseradish peroxidase C and the substrate benzhydroxamic acid determined by X-ray crystallography. , 1998, Biochemistry.

[35]  P. Schleyer.  Encyclopedia of computational chemistry , 1998 .

[36]  P. Kollman,et al.  Encyclopedia of computational chemistry , 1998 .

[37]  D. J. Schuller,et al.  Crystal structure of horseradish peroxidase C at 2.15 Å resolution , 1997, Nature Structural Biology.

[38]  W. C. Still,et al.  The GB/SA Continuum Model for Solvation. A Fast Analytical Method for the Calculation of Approximate Born Radii , 1997 .

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

[40]  S. Sridharan,et al.  A rapid method for calculating derivatives of solvent accessible surface areas of molecules , 1995, J. Comput. Chem..

[41]  P. Kollman,et al.  A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules , 1995 .

[42]  S. Subramaniam,et al.  Treatment of electrostatic effects in proteins: Multigrid‐based newton iterative method for solution of the full nonlinear poisson–boltzmann equation , 1994, Proteins.

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

[44]  B. Tidor,et al.  Do salt bridges stabilize proteins? A continuum electrostatic analysis , 1994, Protein science : a publication of the Protein Society.

[45]  P. Kollman,et al.  Protein structure prediction with a combined solvation free energy-molecular mechanics force field , 1993 .

[46]  P A Kollman,et al.  Absolute and relative binding free energy calculations of the interaction of biotin and its analogs with streptavidin using molecular dynamics/free energy perturbation approaches , 1993, Proteins.

[47]  J. Andrew McCammon,et al.  Computation of electrostatic forces on solvated molecules using the Poisson-Boltzmann equation , 1993 .

[48]  M. Sundaralingam,et al.  Structure of the oxidized long‐chain flavodoxin from anabaena 7120 at 2 å resolution , 1992, Protein science : a publication of the Protein Society.

[49]  F A Quiocho,et al.  Target enzyme recognition by calmodulin: 2.4 A structure of a calmodulin-peptide complex. , 1992, Science.

[50]  Klaus Schulten,et al.  Molecular Dynamics Simulations in Heterogeneous Dielectrica and Debye-Hückel Media - Application to the Protein Bovine Pancreatic Trypsin Inhibitor , 1992 .

[51]  R. Zauhar,et al.  The incorporation of hydration forces determined by continuum electrostatics into molecular mechanics simulations , 1991 .

[52]  B. Honig,et al.  A rapid finite difference algorithm, utilizing successive over‐relaxation to solve the Poisson–Boltzmann equation , 1991 .

[53]  Kim A. Sharp,et al.  Incorporating solvent and ion screening into molecular dynamics using the finite‐difference Poisson–Boltzmann method , 1991 .

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

[55]  G. Brayer,et al.  High-resolution three-dimensional structure of horse heart cytochrome c. , 1990, Journal of molecular biology.

[56]  J. A. McCammon,et al.  Calculating electrostatic forces from grid‐calculated potentials , 1990 .

[57]  B Honig,et al.  Electrical potentials in trypsin isozymes. , 1989, Biochemistry.

[58]  Wilfred F. van Gunsteren,et al.  Computer Simulation of Biomolecular Systems: Theoretical and Experimental Applications , 1989 .

[59]  M. Karplus,et al.  Parametrization of the friction constant for stochastic simulations of polymers , 1988 .

[60]  C. Bugg,et al.  Structure of ubiquitin refined at 1.8 A resolution. , 1987, Journal of molecular biology.

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

[62]  M. L. Connolly.  Solvent-accessible surfaces of proteins and nucleic acids. , 1983, Science.

[63]  M. Karplus,et al.  CHARMM: A program for macromolecular energy, minimization, and dynamics calculations , 1983 .

[64]  A. Szabó,et al.  Model-free approach to the interpretation of nuclear magnetic resonance relaxation in macromolecules. 1. Theory and range of validity , 1982 .

[65]  G. Ciccotti,et al.  Numerical Integration of the Cartesian Equations of Motion of a System with Constraints: Molecular Dynamics of n-Alkanes , 1977 .

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