title: Accurate Calculation of Hydration Free Energies using Pair-Specific Lennard-Jones Parameters in the CHARMM Drude Polarizable Force Field.
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.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, 20 Penn Street, Baltimore, MD 21201, and the Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57 Street, Chicago, IL 60637.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Baker
authors.forename: Pedro E M
authors.initials: PE
authors.lastname: Lopes
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhu
authors.forename: Benoît
authors.initials: B
authors.lastname: Roux
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Mackerell
references.citation: J Comput Chem. 2004 Apr 15;25(5):660-8
references.pmid: 14978709
references.citation: J Comput Chem. 2004 Jan 15;25(1):1-15
references.pmid: 14634989
references.citation: Structure. 2006 Mar;14(3):437-49
references.pmid: 16531228
references.citation: J Phys Chem B. 2007 Mar 8;111(9):2242-54
references.pmid: 17291029
references.citation: J Comput Chem. 2002 Jan 30;23(2):199-213
references.pmid: 11924734
references.citation: J Comput Chem. 2009 Jul 30;30(10):1545-614
references.pmid: 19444816
references.citation: Biochemistry. 1981 Feb 17;20(4):849-55
references.pmid: 7213619
references.citation: Trends Pharmacol Sci. 2002 Jun;23(6):281-7
references.pmid: 12084634
references.citation: J Phys Chem B. 2005 Oct 13;109(40):18988-99
references.pmid: 16853445
references.citation: J Phys Chem B. 2006 Jun 15;110(23):11571-81
references.pmid: 16771434
references.citation: J Comput Chem. 2007 Feb;28(3):689-97
references.pmid: 17195160
references.citation: Bioorg Med Chem. 2008 May 15;16(10):5733-42
references.pmid: 18406153
references.citation: J Chem Theory Comput. 2005 Jan;1(1):153-68
references.pmid: 26641126
references.citation: J Comput Chem. 2009 Sep;30(12):1821-38
references.pmid: 19090564
references.citation: J Am Chem Soc. 2002 Dec 18;124(50):14917-21
references.pmid: 12475333
references.citation: J Chem Theory Comput. 2007 Mar;3(2):530-48
references.pmid: 26637033
references.citation: Nature. 2002 Nov 7;420(6911):102-6
references.pmid: 12422224
references.citation: J Chem Theory Comput. 2005 Nov;1(6):1133-52
references.pmid: 26631657
references.citation: J Mol Biol. 2000 Sep 15;302(2):395-410
references.pmid: 10970741
references.citation: J Chem Theory Comput. 2006 Nov;2(6):1587-97
references.pmid: 26627029
references.citation: Phys Chem Chem Phys. 2005 Apr 7;7(7):1432-40
references.pmid: 19787965
references.citation: J Chem Theory Comput. 2005 Jan;1(1):169-80
references.pmid: 26641127
references.citation: J Chem Theory Comput. 2007 May;3(3):1120-33
references.pmid: 26627431
references.citation: J Phys Chem B. 2008 Jul 17;112(28):8298-310
references.pmid: 18570394
references.citation: J Chem Theory Comput. 2007;3(6):1927-1946
references.pmid: 18802495
references.citation: J Chem Theory Comput. 2006 Jul;2(4):947-55
references.pmid: 26633054
references.citation: Science. 1996 Jan 12;271(5246):163-8
references.pmid: 8539615
references.citation: J Comput Chem. 2004 Oct;25(13):1584-604
references.pmid: 15264253
references.citation: Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9459-64
references.pmid: 10449714
references.citation: J Chem Theory Comput. 2006 Jan;2(1):128-39
references.pmid: 26626387
references.citation: J Phys Chem B. 2006 Sep 7;110(35):17616-26
references.pmid: 16942107
references.citation: Proc Natl Acad Sci U S A. 1987 May;84(10):3086-90
references.pmid: 3472198
references.citation: J Phys Chem B. 2008 Mar 20;112(11):3509-21
references.pmid: 18302362
references.citation: J Chem Phys. 2004 Oct 8;121(14):6998-7008
references.pmid: 15473761
references.citation: Chemphyschem. 2006 Mar 13;7(3):671-8
references.pmid: 16514695
references.citation: J Phys Chem A. 2005 Oct 6;109(39):8893-903
references.pmid: 16834293
references.citation: J Phys Chem B. 2006 Jun 8;110(22):10997-1004
references.pmid: 16771353
references.citation: Theor Chem Acc. 2009 Sep;124(1-2):11-28
references.pmid: 20577578
references.citation: J Comput Chem. 2004 Oct;25(13):1656-76
references.pmid: 15264259
references.citation: J Chem Phys. 2020 Sep 21;153(11):114108
references.pmid: 32962358
references.citation: J Chem Theory Comput. 2005 Jul;1(4):694-715
references.pmid: 26641692
references.citation: J Chem Phys. 2005 Apr 1;122(13):134508
references.pmid: 15847482
references.citation: J Comput Chem. 2004 Sep;25(12):1504-14
references.pmid: 15224394
references.citation: J Phys Chem B. 2007 Mar 22;111(11):2873-85
references.pmid: 17388420
references.citation: Biochemistry. 1978 Jan 10;17(1):201-4
references.pmid: 618544