Accuracy of free energies of hydration using CM1 and CM3 atomic charges

Absolute free energies of hydration (ΔGhyd) have been computed for 25 diverse organic molecules using partial atomic charges derived from AM1 and PM3 wave functions via the CM1 and CM3 procedures of Cramer, Truhlar, and coworkers. Comparisons are made with results using charges fit to the electrostatic potential surface (EPS) from ab initio 6‐31G* wave functions and from the OPLS‐AA force field. OPLS Lennard–Jones parameters for the organic molecules were used together with the TIP4P water model in Monte Carlo simulations with free energy perturbation theory. Absolute free energies of hydration were computed for OPLS united‐atom and all‐atom methane by annihilating the solutes in water and in the gas phase, and absolute ΔGhyd values for all other molecules were computed via transformation to one of these references. Optimal charge scaling factors were determined by minimizing the unsigned average error between experimental and calculated hydration free energies. The PM3‐based charge models do not lead to lower average errors than obtained with the EPS charges for the subset of 13 molecules in the original study. However, improvement is obtained by scaling the CM1A partial charges by 1.14 and the CM3A charges by 1.15, which leads to average errors of 1.0 and 1.1 kcal/mol for the full set of 25 molecules. The scaled CM1A charges also yield the best results for the hydration of amides including the E/Z free‐energy difference for N‐methylacetamide in water. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1322–1332, 2004

[1]  W. L. Jorgensen,et al.  Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids , 1996 .

[2]  U Stocker,et al.  Molecular dynamics simulation of hen egg white lysozyme: A test of the GROMOS96 force field against nuclear magnetic resonance data , 2000, Proteins.

[3]  B. Honig,et al.  New Model for Calculation of Solvation Free Energies: Correction of Self-Consistent Reaction Field Continuum Dielectric Theory for Short-Range Hydrogen-Bonding Effects , 1996 .

[4]  R. Wolfenden,et al.  Influences of solvent water on protein folding: free energies of solvation of cis and trans peptides are nearly identical. , 1988, Biochemistry.

[5]  R. Wolfenden,et al.  Interaction of the peptide bond with solvent water: a vapor phase analysis. , 1978, Biochemistry.

[6]  Arieh Ben-Naim,et al.  Solvation thermodynamics of nonionic solutes , 1984 .

[7]  Heather A. Carlson,et al.  Accuracy of free energies of hydration for organic molecules from 6‐31g*‐derived partial charges , 1993, J. Comput. Chem..

[8]  Peter A. Kollman,et al.  Solvation Free Energies of Amides and Amines: Disagreement between Free Energy Calculations and Experiment , 1995 .

[9]  William L. Jorgensen,et al.  Gas‐phase and liquid‐state properties of esters, nitriles, and nitro compounds with the OPLS‐AA force field , 2001, J. Comput. Chem..

[10]  R. Levy,et al.  Enthalpy−Entropy and Cavity Decomposition of Alkane Hydration Free Energies: Numerical Results and Implications for Theories of Hydrophobic Solvation , 2000 .

[11]  George A. Kaminski,et al.  Development of an Accurate and Robust Polarizable Molecular Mechanics Force Field from ab Initio Quantum Chemistry , 2004 .

[12]  Modesto Orozco,et al.  Theoretical study of N-methylacetamide in vacuum and aqueous solution : implications for the peptide bond isomerization , 1993 .

[13]  William L. Jorgensen,et al.  Improved convergence of binding affinities with free energy perturbation: Application to nonpeptide ligands with pp60src SH2 domain , 2001, J. Comput. Aided Mol. Des..

[14]  Norman L. Allinger,et al.  Molecular Mechanics (MM4) Calculations on Amides , 2002 .

[15]  William L. Jorgensen,et al.  Cis-trans energy difference for the peptide bond in the gas phase and in aqueous solution , 1988 .

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

[17]  William L. Jorgensen,et al.  A Quantum Mechanical and Molecular Mechanical Method Based on CM1A Charges: Applications to Solvent Effects on Organic Equilibria and Reactions , 1998 .

[18]  William L. Jorgensen,et al.  Free Energies of Hydration and Pure Liquid Properties of Hydrocarbons from the OPLS All-Atom Model , 1994 .

[19]  R. Zwanzig.  High‐Temperature Equation of State by a Perturbation Method. I. Nonpolar Gases , 1954 .

[20]  Donald G. Truhlar,et al.  Parameterization of charge model 3 for AM1, PM3, BLYP, and B3LYP , 2003, J. Comput. Chem..

[21]  Harry A. Stern,et al.  Fluctuating Charge, Polarizable Dipole, and Combined Models: Parameterization from ab Initio Quantum Chemistry , 1999 .

[22]  Pengyu Y. Ren,et al.  Consistent treatment of inter‐ and intramolecular polarization in molecular mechanics calculations , 2002, J. Comput. Chem..

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

[24]  William L. Jorgensen,et al.  OPLS ALL-ATOM MODEL FOR AMINES : RESOLUTION OF THE AMINE HYDRATION PROBLEM , 1999 .

[25]  Michael H. Abraham,et al.  Hydrogen bonding. Part 34. The factors that influence the solubility of gases and vapours in water at 298 K, and a new method for its determination , 1994 .

[26]  W. L. Jorgensen,et al.  Monte Carlo simulation of differences in free energies of hydration , 1985 .

[27]  David J. Giesen,et al.  Class IV charge models: A new semiempirical approach in quantum chemistry , 1995, J. Comput. Aided Mol. Des..

[28]  Charles L. Brooks,et al.  CHARMM fluctuating charge force field for proteins: I parameterization and application to bulk organic liquid simulations , 2004, J. Comput. Chem..

[29]  William L. Jorgensen,et al.  Free energy of TIP4P water and the free energies of hydration of CH4 and Cl- from statistical perturbation theory , 1989 .

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

[31]  P. Kollman,et al.  A well-behaved electrostatic potential-based method using charge restraints for deriving atomic char , 1993 .

[32]  J. Jadżyn,et al.  DIELECTRIC PROPERTIES AND MOLECULAR STRUCTURE OF AMIDE SOLUTIONS. 1. N-METHYLACETAMIDE IN CARBON TETRACHLORIDE , 1983 .

[33]  William L. Jorgensen,et al.  Free Energies of Hydration for Organic Molecules from Monte Carlo Simulations , 1995 .

[34]  William L. Jorgensen,et al.  QM/MM Simulations for Diels−Alder Reactions in Water: Contribution of Enhanced Hydrogen Bonding at the Transition State to the Solvent Effect† , 2002 .

[35]  William L. Jorgensen,et al.  Aromatic-aromatic interactions: free energy profiles for the benzene dimer in water, chloroform, and liquid benzene , 1990 .

[36]  William L. Jorgensen,et al.  Ab Initio Study Of Hydrogen-Bonded Complexes Of Small Organic Molecules With Water , 1998 .

[37]  Arnold T. Hagler,et al.  Derivation of Class II Force Fields. 7. Nonbonded Force Field Parameters for Organic Compounds , 1999 .

[38]  B. Honig,et al.  Accurate First Principles Calculation of Molecular Charge Distributions and Solvation Energies from Ab Initio Quantum Mechanics and Continuum Dielectric Theory , 1994 .

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

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

[41]  Ronald M. Levy,et al.  SOLVATION FREE ENERGIES OF SMALL AMIDES AND AMINES FROM MOLECULAR DYNAMICS/FREE ENERGY PERTURBATION SIMULATIONS USING PAIRWISE ADDITIVE AND MANY-BODY POLARIZABLE POTENTIALS , 1995 .

[42]  William L. Jorgensen,et al.  Perfluoroalkanes: Conformational Analysis and Liquid-State Properties from ab Initio and Monte Carlo Calculations , 2001 .

[43]  Sture Forsén,et al.  The barrier to internal rotation in monosubstituted amides , 1971 .