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

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)144-153
Number of pages10
JournalJournal of Molecular Graphics and Modelling
Publication statusPublished - 2016 Sept 1


  • Drug design
  • Fragment molecular orbital method
  • Hydration of ligands
  • Influenza virus neuraminidase
  • N-acetylneuraminic acid
  • Oseltamivir
  • Solvation energy
  • Zanamivir


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