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Journal of Biomedicine and Biotechnology
Volume 2012 (2012), Article ID 236157, 11 pages
Review Article

Biological Applications of Hybrid Quantum Mechanics/Molecular Mechanics Calculation

1Graduate School of Pure and Applied Sciences, University of Tsukuba, Tsukuba Science City, Tsukuba 305-857, Japan
2Graduate School of Life Science, University of Hyogo, 3-2-1 Koto, Kamigori-cho, Ako-gun, Hyogo 678-1297, Japan

Received 15 July 2011; Revised 27 October 2011; Accepted 11 November 2011

Academic Editor: Sergio Pantano

Copyright © 2012 Jiyoung Kang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Since in most cases biological macromolecular systems including solvent water molecules are remarkably large, the computational costs of performing ab initio calculations for the entire structures are prohibitive. Accordingly, QM calculations that are jointed with MM calculations are crucial to evaluate the long-range electrostatic interactions, which significantly affect the electronic structures of biological macromolecules. A UNIX-shell-based interface program connecting the quantum mechanics (QMs) and molecular mechanics (MMs) calculation engines, GAMESS and AMBER, was developed in our lab. The system was applied to a metalloenzyme, azurin, and PU.1-DNA complex; thereby, the significance of the environmental effects on the electronic structures of the site of interest was elucidated. Subsequently, hybrid QM/MM molecular dynamics (MD) simulation using the calculation system was employed for investigation of mechanisms of hydrolysis (editing reaction) in leucyl-tRNA synthetase complexed with the misaminoacylated t R N A L e u , and a novel mechanism of the enzymatic reaction was revealed. Thus, our interface program can play a critical role as a powerful tool for state-of-the-art sophisticated hybrid ab initio QM/MM MD simulations of large systems, such as biological macromolecules.