Hydration of ligands of influenza virus neuraminidase studied by the fragment molecular orbital method

Kana Tokuda, Chiduru Watanabe, Yoshio Okiyama, Yuji Mochizuki, Kaori Fukuzawa, Yuto Komeiji

研究成果: Article査読

7 被引用数 (Scopus)

抄録

The fragment molecular orbital (FMO) method was applied to quantum chemical calculations of neuramic acid, the natural substrate of the influenza virus neuraminidase, and two of its competitive inhibitors, Oseltamivir (Tamiful®) and Zanamivir (Relenza®), to investigate their hydrated structures and energetics. Each of the three ligands was immersed in an explicit water solvent, geometry-optimized by classical MM and QM/MM methods, and subjected to FMO calculations with 2-, 3-, and 4-body corrections under several fragmentation options. The important findings were that QM/MM optimization was preferable to obtain reliable hydrated structures of the ligands, that the 3-body correction was important for quantitative evaluation of the solvation energy, and that the dehydration effect was most remarkable near the hydrophobic sections of the ligands. In addition, the hydration energy calculated by the explicit solvent was compared with the hydration free energy calculated by the implicit solvent via the Poisson-Boltzmann equation, and the two showed a fairly good correlation. These findings will serve as useful information for rapid drug design.

本文言語English
ページ(範囲)144-153
ページ数10
ジャーナルJournal of Molecular Graphics and Modelling
69
DOI
出版ステータスPublished - 2016 9 1
外部発表はい

ASJC Scopus subject areas

  • 分光学
  • 物理化学および理論化学
  • コンピュータ グラフィックスおよびコンピュータ支援設計
  • 材料化学

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