Reoptimized interaction parameters for the peptide‐backbone model compound N‐methylacetamide in the GROMOS force field: Influence on the folding properties of two beta‐peptides in methanol

Considering N‐methylacetamide (NMA) as a model compound, new interaction parameters are developed for the amide function in the GROMOS force field that are compatible with the recently derived 53A6OXY parameter set for oxygen‐containing chemical functions. The resulting set, referred to as 53A6OXY+A, represents an improvement over earlier GROMOS force‐field versions in the context of the pure‐liquid properties of NMA, including the density, heat of vaporization, dielectric permittivity, self‐diffusion constant and viscosity, as well as in terms of the Gibbs hydration free energy of this molecule. Assuming that NMA represents an adequate model compound for the backbone of peptides, 53A6OXY+A may be expected to also provide an improved description of polypeptide chains. As an initial test, simulations are reported for two β‐peptides characterized by very different folding properties in methanol. For these systems, earlier force‐field versions provided good agreement with experimental NMR data, and the test shows that the improved description achieved in the context of NMA is not accompanied by any deterioration in the representation of the conformational properties of these peptides. © 2012 Wiley Periodicals, Inc.

[1]  J. A. Barker,et al.  Monte Carlo studies of the dielectric properties of water-like models , 1973 .

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

[3]  Markus Christen,et al.  The GROMOS software for biomolecular simulation: GROMOS05 , 2005, J. Comput. Chem..

[4]  Giovanni Bussi,et al.  Ensemble of transition state structures for the cis-trans isomerization of N-methylacetamide. , 2009, The journal of physical chemistry. B.

[5]  B. Jaun,et al.  Probing the Helical Secondary Structure of Short‐Chain β‐Peptides , 1996 .

[6]  Philippe H Hünenberger,et al.  Ball-and-Stick Local Elevation Umbrella Sampling: Molecular Simulations Involving Enhanced Sampling within Conformational or Alchemical Subspaces of Low Internal Dimensionalities, Minimal Irrelevant Volumes, and Problem-Adapted Geometries. , 2010, Journal of chemical theory and computation.

[7]  Philippe H. Hünenberger,et al.  Using the local elevation method to construct optimized umbrella sampling potentials: Calculation of the relative free energies and interconversion barriers of glucopyranose ring conformers in water , 2010, J. Comput. Chem..

[8]  Gregory D. Hawkins,et al.  Extension of the platform of applicability of the SM5.42R universal solvation model , 1999 .

[9]  Alexander D. MacKerell,et al.  Re-evaluation of the reported experimental values of the heat of vaporization of N-methylacetamide. , 2008, Journal of chemical theory and computation.

[10]  Xiao-Nan Jiang,et al.  Rapid prediction of the hydrogen bond cooperativity in N-methylacetamide chains. , 2009, Chemphyschem : a European journal of chemical physics and physical chemistry.

[11]  Alexander D. MacKerell.  Empirical force fields for biological macromolecules: Overview and issues , 2004, J. Comput. Chem..

[12]  X. Daura,et al.  Reversible peptide folding in solution by molecular dynamics simulation. , 1998, Journal of molecular biology.

[13]  John C. Slater,et al.  The Van Der Waals Forces in Gases , 1931 .

[14]  X. Daura,et al.  The beta-peptide hairpin in solution: conformational study of a beta-hexapeptide in methanol by NMR spectroscopy and MD simulation. , 2001, Journal of the American Chemical Society.

[15]  The effect of using a polarizable solvent model upon the folding equilibrium of different β-peptides , 2011 .

[16]  Alan E. Mark,et al.  The GROMOS96 Manual and User Guide , 1996 .

[17]  R. Bechmann,et al.  Numerical data and functional relationships in science and technology , 1969 .

[18]  M. Bahri,et al.  X-ray scattering and density-functional theory calculations to study the presence of hydrogen-bonded clusters in liquid N-methylacetamide. , 2005, The Journal of chemical physics.

[19]  D. K. Hazra,et al.  Excess Molar Volumes, Viscosity Deviations, and Isentropic Compressibility Changes in Binary Mixtures of N-Methylacetamide + 2-Methoxyethanol and N-Methylacetamide + Water at (308.15, 313.15, and 318.15) K , 2002 .

[20]  Enhanced Conformational Sampling in Molecular Dynamics Simulations of Solvated Peptides: Fragment-Based Local Elevation Umbrella Sampling. , 2010, Journal of chemical theory and computation.

[21]  Chris Oostenbrink,et al.  A biomolecular force field based on the free enthalpy of hydration and solvation: The GROMOS force‐field parameter sets 53A5 and 53A6 , 2004, J. Comput. Chem..

[22]  Alexander D. MacKerell,et al.  All-atom empirical potential for molecular modeling and dynamics studies of proteins. , 1998, The journal of physical chemistry. B.

[23]  A. M. Zaichikov.  Structural thermodynamic parameters and intermolecular interactions in aqueous solutions of secondary amides , 2007 .

[24]  A. B. Haan,et al.  Excess Enthalpies for Various Binary Mixtures with N-Methylacetamide or Acetic Anhydride , 1996 .

[25]  Andreas P. Eichenberger,et al.  Definition and testing of the GROMOS force-field versions 54A7 and 54B7 , 2011, European Biophysics Journal.

[26]  W. V. van Gunsteren,et al.  Validation of the GROMOS 54A7 Force Field with Respect to β-Peptide Folding. , 2011, Journal of chemical theory and computation.

[27]  Ping Qian,et al.  Molecular dynamics simulations of N-methylacetamide (NMA) in water by the ABEEM/MM model , 2009 .

[28]  X. Daura,et al.  Studying the Stability of a Helical β‐Heptapeptide by Molecular Dynamics Simulations , 1997 .

[29]  Chris Oostenbrink,et al.  An improved nucleic acid parameter set for the GROMOS force field , 2005, J. Comput. Chem..

[30]  Wilfred F van Gunsteren,et al.  On the Calculation of the Dielectric Permittivity and Relaxation of Molecular Models in the Liquid Phase. , 2011, Journal of chemical theory and computation.

[31]  Wilfred F. van Gunsteren,et al.  The effect of force-field parameters on properties of liquids: Parametrization of a simple three-site model for methanol , 2000 .

[32]  W. V. van Gunsteren,et al.  New Interaction Parameters for Oxygen Compounds in the GROMOS Force Field: Improved Pure-Liquid and Solvation Properties for Alcohols, Ethers, Aldehydes, Ketones, Carboxylic Acids, and Esters. , 2011, Journal of chemical theory and computation.

[33]  Haiyan Liu,et al.  Refining the description of peptide backbone conformations improves protein simulations using the GROMOS 53A6 force field , 2009, J. Comput. Chem..

[34]  F. Eirich,et al.  Properties of amides in aqueous solution. I. Viscosity and density changes of amide-water systems. An analysis of volume deficiencies of mixtures based on molecular size differences (mixing of hard spheres) , 1968 .

[35]  Ab initio and empirical model MD simulation studies of solvent effects on the properties of N-methylacetamide along a cis-trans isomerization pathway. , 2006, The journal of physical chemistry. B.

[36]  Wilfred F. van Gunsteren,et al.  A generalized reaction field method for molecular dynamics simulations , 1995 .

[37]  J. Crain,et al.  Solution structure of the aqueous model peptide N-methylacetamide. , 2006, The journal of physical chemistry. B.

[38]  Alexander D. MacKerell,et al.  Understanding the dielectric properties of liquid amides from a polarizable force field. , 2008, The journal of physical chemistry. B.

[39]  Donald G. Truhlar,et al.  Universal Quantum Mechanical Model for Solvation Free Energies Based on Gas-Phase Geometries , 1998 .

[40]  Roberto D. Lins,et al.  A new GROMOS force field for hexopyranose‐based carbohydrates , 2005, J. Comput. Chem..

[41]  H. Berendsen.  Simulating the Physical World , 2004 .

[42]  K. Jyothi,et al.  Acoustic, viscometric and volumetric properties of binary mixtures of N-methylacetamide with some aliphatic mono and di alkyl amines at T = 308.15 K , 2010 .

[43]  Wilfred F. van Gunsteren,et al.  An improved GROMOS96 force field for aliphatic hydrocarbons in the condensed phase , 2001, J. Comput. Chem..

[44]  Gertrud Beggerow,et al.  Numerical data and functional relationships in science and technology , 1976 .

[45]  J. Davenport.  Editor , 1960 .

[46]  Haoran Li,et al.  All-atom simulation and excess properties study on intermolecular interactions of amide–water system , 2008 .

[47]  W. V. van Gunsteren,et al.  Temperature dependence of the dielectric permittivity of acetic acid, propionic acid and their methyl esters: a molecular dynamics simulation study. , 2012, Chemphyschem : a European journal of chemical physics and physical chemistry.

[48]  R. H. Graves,et al.  Solvents Having High Dielectric Constants. II. Solutions of Alkali Halides in N-Methylacetamide from 30 to 60°1a,b , 1955 .

[49]  Alexander D. MacKerell,et al.  Importance of the CMAP correction to the CHARMM22 protein force field: dynamics of hen lysozyme. , 2006, Biophysical journal.

[50]  Riccardo Baron,et al.  Conformational properties of glucose-based disaccharides investigated using molecular dynamics simulations with local elevation umbrella sampling. , 2010, Carbohydrate research.