Interaction Entropy for Computational Alanine Scanning

Yuna Yan, Maoyou Yang, Chang G. Ji, John Z.H. Zhang

Research output: Contribution to journalArticlepeer-review


The theoretical calculation of protein-protein binding free energy is a grand challenge in computational biology. Accurate prediction of critical residues along with their specific and quantitative contributions to protein-protein binding free energy is extremely helpful to reveal binding mechanisms and identify drug-like molecules that alter protein-protein interactions. In this paper, we propose an interaction entropy approach combined with the molecular mechanics/generalized Born surface area (MM/GBSA) method for solvation to compute residue-specific protein-protein binding free energy. In the current approach, the entropic loss in binding free energy of individual residues is explicitly computed from moledular dynamics (MD) simulation by using the interaction entropy method. In this approach the entropic contribution to binding free energy is determined from fluctuation of the interaction in MD simulation. Studies for an extensive set of realistic protein-protein interaction systems showed that by including the entropic contribution, the computed residue-specific binding free energies are in better agreement with the corresponding experimental data.

Original languageEnglish (US)
Pages (from-to)1112-1122
Number of pages11
JournalJournal of Chemical Information and Modeling
Issue number5
StatePublished - May 22 2017

ASJC Scopus subject areas

  • General Chemistry
  • General Chemical Engineering
  • Computer Science Applications
  • Library and Information Sciences


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