Protein's native structure is dynamically stabilized by electronic polarization

Li L. Duan, Ye Mei, Qing G. Zhang, Bo Tang, John Z.H. Zhang

Research output: Contribution to journalArticle

Abstract

In this paper, molecular dynamics (MD) simulations were performed for a number of benchmark proteins using both the standard assisted model building with energy refinement (AMBER) charge and the dynamically adjusted polarized protein-specific charge (DPPC) from quantum fragment calculations to provide accurate electrostatic interactions. Our result shows that proteins' dynamic structures drifted away from the native structures in simulations under standard (nonpolarizable) AMBER force field. For comparison, proteins' native structures were dynamically stable after a long time simulation under DPPC. The free energy landscape reveals that the native structure is the lowest energy conformation under DPPC, while it is not under standard AMBER charge. To further investigate the polarization effect on the stability of native structures of proteins, we restarted from some decoy structures generated from simulations using standard AMBER charges and then carried out further MD simulation using DPPC to refine those structures. Our study shows that the native structures from these decoy structures can be mostly recovered using DPPC and that the dynamic structures with the highest population in cluster analysis are in close agreement with the corresponding native structures. The current study demonstrates the importance of electronic polarization of protein in stabilizing the native structure.

Original languageEnglish (US)
Article number1440005
JournalJournal of Theoretical and Computational Chemistry
Volume13
Issue number3
DOIs
StatePublished - May 2014

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Keywords

  • Decoy structure
  • Force field
  • Native structure
  • Polarization
  • Polarized protein-specific charge (DPPC)
  • Stabilization

ASJC Scopus subject areas

  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Computational Theory and Mathematics

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