Over-Destabilization of Protein-Protein Interaction in Generalized Born Model and Utility of Energy Density Integration Cutoff

Yukinobu Mizuhara, Dan Parkin, Koji Umezawa, Jun Ohnuki, Mitsunori Takano*

*この研究の対応する著者

研究成果: Article査読

6 被引用数 (Scopus)

抄録

The generalize Born (GB) model is frequently used in MD simulations of biomolecular systems in aqueous solution. The GB model is usually based on the so-called Coulomb field approximation (CFA) for the energy density integration. In this study, we report that the GB model with CFA overdestabilizes the long-range electrostatic attraction between oppositely charged molecules (ionic bond forming two-helix system and kinesin-tubulin system) when the energy density integration cutoff, rmax, which is used to calculate the Born energy, is set to a large value. We show that employing large rmax, which is usually expected to make simulation results more accurate, worsens the accuracy so that the attraction is changed into repulsion. It is demonstrated that the overdestabilization is caused by the overestimation of the desolvation penalty upon binding that originates from CFA. We point out that the overdestabilization can be corrected by employing a relatively small cutoff (rmax = 10-15 Å), affirming that the GB models, even with CFA, can be used as a powerful tool to theoretically study the protein-protein interaction, particularly on its dynamical aspect, such as binding and unbinding.

本文言語English
ページ(範囲)4669-4677
ページ数9
ジャーナルJournal of Physical Chemistry B
121
18
DOI
出版ステータスPublished - 2017 5 11

ASJC Scopus subject areas

  • 物理化学および理論化学
  • 表面、皮膜および薄膜
  • 材料化学

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