Fragment Molecular Orbital Calculations with Implicit Solvent Based on the Poisson-Boltzmann Equation: II. Protein and Its Ligand-Binding System Studies

Yoshio Okiyama, Chiduru Watanabe, Kaori Fukuzawa, Yuji Mochizuki, Tatsuya Nakano, Shigenori Tanaka

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

In this study, the electronic properties of bioactive proteins were analyzed using an ab initio fragment molecular orbital (FMO) methodology in solution: coupling with an implicit solvent model based on the Poisson-Boltzmann surface area called as FMO-PBSA. We investigated the solvent effects on practical and heterogeneous targets with uneven exposure to solvents unlike deoxyribonucleic acid analyzed in our recent study. Interfragment interaction energy (IFIE) and its decomposition analyses by FMO-PBSA revealed solvent-screening mechanisms that affect local stability inside ubiquitin protein: the screening suppresses excessiveness in bare charge-charge interactions and enables an intuitive IFIE analysis. The electrostatic character and associated solvation free energy also give consistent results as a whole to previous studies on the explicit solvent model. Moreover, by using the estrogen receptor alpha (ERα) protein bound to ligands, we elucidated the importance of specific interactions that depend on the electric charge and activatability as agonism/antagonism of the ligand while estimating the influences of the implicit solvent on the ligand and helix-12 bindings. The predicted ligand-binding affinities of bioactive compounds to ERα also show a good correlation with their in vitro activities. The FMO-PBSA approach would thus be a promising tool both for biological and pharmaceutical research targeting proteins.

Original languageEnglish
Pages (from-to)957-973
Number of pages17
JournalJournal of Physical Chemistry B
Volume123
Issue number5
DOIs
Publication statusPublished - 2019 Feb 7
Externally publishedYes

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

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