Accessing the applicability of polarized protein-specific charge in linear interaction energy analysis

Xiangyu Jia, Juan Zeng, John Z.H. Zhang, Ye Mei

Research output: Contribution to journalArticle

Abstract

The reliability of the linear interaction energy (LIE) depends on the atomic charge model used to delineate the Coulomb interaction between the ligand and its environment. In this work, the polarized protein-specific charge (PPC) implementing a recently proposed fitting scheme has been examined in the LIE calculations of the binding affinities for avidin and β-secretase binding complexes. This charge fitting scheme, termed delta restrained electrostatic potential, bypasses the prevalent numerical difficulty of rank deficiency in electrostatic-potential-based charge fitting methods via a dual-step fitting strategy. A remarkable consistency between the predicted binding affinities and the experimental measurement has been observed. This work serves as a direct evidence of PPC's applicability in rational drug design.

Original languageEnglish (US)
Pages (from-to)737-747
Number of pages11
JournalJournal of Computational Chemistry
Volume35
Issue number9
DOIs
StatePublished - Apr 5 2014

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Keywords

  • avidin
  • charge model
  • force field
  • linear interaction energy
  • polarization
  • β-secretase

ASJC Scopus subject areas

  • Chemistry(all)
  • Computational Mathematics

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