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J Mol Graph Model. 2016 Aug 31;69:144-153. doi: 10.1016/j.jmgm.2016.08.004. [Epub ahead of print]
Hydration of ligands of influenza virus neuraminidase studied by the fragment molecular orbital method.
Tokuda K1, Watanabe C2, Okiyama Y2, Mochizuki Y3, Fukuzawa K4, Komeiji Y5.
Author information
Abstract
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.
Copyright ? 2016 Elsevier Inc. All rights reserved.
KEYWORDS:
Drug design; Fragment molecular orbital method; Hydration of ligands; Influenza virus neuraminidase; N-acetylneuraminic acid; Oseltamivir; Solvation energy; Zanamivir
PMID: 27611645 DOI: 10.1016/j.jmgm.2016.08.004
[PubMed - as supplied by publisher]
Hydration of ligands of influenza virus neuraminidase studied by the fragment molecular orbital method.
Tokuda K1, Watanabe C2, Okiyama Y2, Mochizuki Y3, Fukuzawa K4, Komeiji Y5.
Author information
Abstract
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.
Copyright ? 2016 Elsevier Inc. All rights reserved.
KEYWORDS:
Drug design; Fragment molecular orbital method; Hydration of ligands; Influenza virus neuraminidase; N-acetylneuraminic acid; Oseltamivir; Solvation energy; Zanamivir
PMID: 27611645 DOI: 10.1016/j.jmgm.2016.08.004
[PubMed - as supplied by publisher]