Calculations of Solvation Free Energy through Energy Reweighting from Molecular Mechanics to Quantum Mechanics

Xiangyu Jia, Meiting Wang, Yihan Shao, Gerhard König, Bernard R. Brooks, John Z.H. Zhang, Ye Mei

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)499-511
Number of pages13
JournalJournal of chemical theory and computation
Volume12
Issue number2
DOIs
StatePublished - Feb 9 2016

ASJC Scopus subject areas

  • Computer Science Applications
  • Physical and Theoretical Chemistry

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