Accurate Calculation of Hydration Free Energies Using Pair-Specific Lennard-Jones Parameters in the CHARMM Drude Polarizable Force Field

Overview

Journal J Chem Theory Comput

Publisher American Chemical Society

Specialties Biochemistry
Chemistry

Date 2010 Apr 20

PMID 20401166

Citations 73

Authors

Christopher M Baker

Pedro E M Lopes

Xiao Zhu

Benoit Roux

Alexander D MacKerell Jr

Affiliations

Soon will be listed here.

Abstract

Lennard-Jones (LJ) parameters for a variety of model compounds have previously been optimized within the CHARMM Drude polarizable force field to reproduce accurately pure liquid phase thermodynamic properties as well as additional target data. While the polarizable force field resulting from this optimization procedure has been shown to satisfactorily reproduce a wide range of experimental reference data across numerous series of small molecules, a slight but systematic overestimate of the hydration free energies has also been noted. Here, the reproduction of experimental hydration free energies is greatly improved by the introduction of pair-specific LJ parameters between solute heavy atoms and water oxygen atoms that override the standard LJ parameters obtained from combining rules. The changes are small and a systematic protocol is developed for the optimization of pair-specific LJ parameters and applied to the development of pair-specific LJ parameters for alkanes, alcohols and ethers. The resulting parameters not only yield hydration free energies in good agreement with experimental values, but also provide a framework upon which other pair-specific LJ parameters can be added as new compounds are parametrized within the CHARMM Drude polarizable force field. Detailed analysis of the contributions to the hydration free energies reveals that the dispersion interaction is the main source of the systematic errors in the hydration free energies. This information suggests that the systematic error may result from problems with the LJ combining rules and is combined with analysis of the pair-specific LJ parameters obtained in this work to identify a preliminary improved combining rule.

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References

Al-Matar A, Rockstraw D . A generating equation for mixing rules and two new mixing rules for interatomic potential energy parameters. J Comput Chem. 2004; 25(5):660-8. DOI: 10.1002/jcc.10418. View

Patel S, Brooks 3rd C . CHARMM fluctuating charge force field for proteins: I parameterization and application to bulk organic liquid simulations. J Comput Chem. 2003; 25(1):1-15. DOI: 10.1002/jcc.10355. View

Freddolino P, Arkhipov A, Larson S, McPherson A, Schulten K . Molecular dynamics simulations of the complete satellite tobacco mosaic virus. Structure. 2006; 14(3):437-49. DOI: 10.1016/j.str.2005.11.014. View

Mobley D, Dumont E, Chodera J, Dill K . Comparison of charge models for fixed-charge force fields: small-molecule hydration free energies in explicit solvent. J Phys Chem B. 2007; 111(9):2242-54. DOI: 10.1021/jp0667442. View

Chen I, Yin D, MacKerell Jr A . Combined ab initio/empirical approach for optimization of Lennard-Jones parameters for polar-neutral compounds. J Comput Chem. 2002; 23(2):199-213. DOI: 10.1002/jcc.1166. View

Brooks B, Brooks 3rd C, MacKerell Jr A, Nilsson L, Petrella R, Roux B . CHARMM: the biomolecular simulation program. J Comput Chem. 2009; 30(10):1545-614. PMC: 2810661. DOI: 10.1002/jcc.21287. View

Wolfenden R, Andersson L, Cullis P, Southgate C . Affinities of amino acid side chains for solvent water. Biochemistry. 1981; 20(4):849-55. DOI: 10.1021/bi00507a030. View

Zacharias N, Dougherty D . Cation-pi interactions in ligand recognition and catalysis. Trends Pharmacol Sci. 2002; 23(6):281-7. DOI: 10.1016/s0165-6147(02)02027-8. View

Vorobyov I, Anisimov V, MacKerell Jr A . Polarizable empirical force field for alkanes based on the classical Drude oscillator model. J Phys Chem B. 2006; 109(40):18988-99. DOI: 10.1021/jp053182y. View

10.

Babin V, Baucom J, Darden T, Sagui C . Molecular dynamics simulations of DNA with polarizable force fields: convergence of an ideal B-DNA structure to the crystallographic structure. J Phys Chem B. 2006; 110(23):11571-81. DOI: 10.1021/jp061421r. View

11.

Xu Z, Luo H, Tieleman D . Modifying the OPLS-AA force field to improve hydration free energies for several amino acid side chains using new atomic charges and an off-plane charge model for aromatic residues. J Comput Chem. 2006; 28(3):689-97. DOI: 10.1002/jcc.20560. View

12.

Michielan L, Bacilieri M, Kaseda C, Moro S . Prediction of the aqueous solvation free energy of organic compounds by using autocorrelation of molecular electrostatic potential surface properties combined with response surface analysis. Bioorg Med Chem. 2008; 16(10):5733-42. DOI: 10.1016/j.bmc.2008.03.064. View

13.

Anisimov V, Lamoureux G, Vorobyov I, Huang N, Roux B, MacKerell A . Determination of Electrostatic Parameters for a Polarizable Force Field Based on the Classical Drude Oscillator. J Chem Theory Comput. 2015; 1(1):153-68. DOI: 10.1021/ct049930p. View

14.

Lopes P, Lamoureux G, MacKerell Jr A . Polarizable empirical force field for nitrogen-containing heteroaromatic compounds based on the classical Drude oscillator. J Comput Chem. 2008; 30(12):1821-38. PMC: 2704921. DOI: 10.1002/jcc.21183. View

15.

Tsou L, Tatko C, Waters M . Simple cation-pi interaction between a phenyl ring and a protonated amine stabilizes an alpha-helix in water. J Am Chem Soc. 2002; 124(50):14917-21. DOI: 10.1021/ja026721a. View

16.

Baker C, Grant G . Modeling Aromatic Liquids: Toluene, Phenol, and Pyridine. J Chem Theory Comput. 2015; 3(2):530-48. DOI: 10.1021/ct600218f. View

17.

Snow C, Nguyen H, Pande V, Gruebele M . Absolute comparison of simulated and experimental protein-folding dynamics. Nature. 2002; 420(6911):102-6. DOI: 10.1038/nature01160. View

18.

Kelly C, Cramer C, Truhlar D . SM6: A Density Functional Theory Continuum Solvation Model for Calculating Aqueous Solvation Free Energies of Neutrals, Ions, and Solute-Water Clusters. J Chem Theory Comput. 2015; 1(6):1133-52. DOI: 10.1021/ct050164b. View

19.

Wintjens R, Lievin J, Rooman M, Buisine E . Contribution of cation-pi interactions to the stability of protein-DNA complexes. J Mol Biol. 2000; 302(2):395-410. DOI: 10.1006/jmbi.2000.4040. View

20.

Harder E, Anisimov V, Vorobyov I, Lopes P, Noskov S, MacKerell A . Atomic Level Anisotropy in the Electrostatic Modeling of Lone Pairs for a Polarizable Force Field Based on the Classical Drude Oscillator. J Chem Theory Comput. 2015; 2(6):1587-97. DOI: 10.1021/ct600180x. View