title: Calculations of Solvation Free Energy through Energy Reweighting from Molecular Mechanics to Quantum Mechanics.
abstract: In this work, the solvation free energies of 20 organic molecules from the 4th Statistical Assessment of the Modeling of Proteins and Ligands (SAMPL4) have been calculated. The sampling of phase space is carried out at a molecular mechanical level, and the associated free energy changes are estimated using the Bennett Acceptance Ratio (BAR). Then the quantum mechanical (QM) corrections are computed through the indirect Non-Boltzmann Bennett's acceptance ratio (NBB) or the thermodynamics perturbation (TP) method. We show that BAR+TP gives a minimum analytic variance for the calculated solvation free energy at the Gaussian limit and performs slightly better than NBB in practice. Furthermore, the expense of the QM calculations in TP is only half of that in NBB. We also show that defining the biasing potential as the difference of the solute-solvent interaction energy, instead of the total energy, can converge the calculated solvation free energies much faster but possibly to different values. Based on the experimental solvation free energies which have been published before, it is discovered in this study that BLYP yields better results than MP2 and some other later functionals such as B3LYP, M06-2X, and ωB97X-D.
authors.affiliation: State Key Laboratory of Precision Spectroscopy and Department of Physics and Institute of Theoretical and Computational Science, East China Normal University , Shanghai 200062, China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Precision Spectroscopy and Department of Physics and Institute of Theoretical and Computational Science, East China Normal University , Shanghai 200062, China.
authors.forename: Meiting
authors.initials: M
authors.lastname: Wang
authors.affiliation: Q-Chem Inc., 6601 Owens Drive, Suite 105, Pleasanton, California 94588, United States.
authors.forename: Yihan
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Laboratory of Computational Biology, National Institutes of Health, National Heart, Lung and Blood Institute , 5635 Fishers Lane, T-900 Suite, Rockville, Maryland 20852, United States.
authors.forename: Gerhard
authors.initials: G
authors.lastname: König
authors.affiliation: Laboratory of Computational Biology, National Institutes of Health, National Heart, Lung and Blood Institute , 5635 Fishers Lane, T-900 Suite, Rockville, Maryland 20852, United States.
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Brooks
authors.affiliation: State Key Laboratory of Precision Spectroscopy and Department of Physics and Institute of Theoretical and Computational Science, East China Normal University , Shanghai 200062, China.|NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai 200062, China.
authors.forename: John Z H
authors.initials: JZ
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Precision Spectroscopy and Department of Physics and Institute of Theoretical and Computational Science, East China Normal University , Shanghai 200062, China.|NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai 200062, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Mei
mesh_terms: D008024:Ligands; D008958:Models, Molecular; D011506:Proteins / Q000737:chemistry; D011789:Quantum Theory; D012997:Solvents / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D008024:Ligands; D011506:Proteins; D012997:Solvents