title: Biological applications of hybrid quantum mechanics/molecular mechanics calculation.
abstract: 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 tRNA(Leu), 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.
authors.affiliation: Graduate School of Pure and Applied Sciences, University of Tsukuba, Tsukuba Science City, Tsukuba, Japan.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kang
authors.forename: Yohsuke
authors.initials: Y
authors.lastname: Hagiwara
authors.forename: Masaru
authors.initials: M
authors.lastname: Tateno
mesh_terms: D001400:Azurin / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D019295:Computational Biology / Q000379:methods*; D006868:Hydrolysis; D007935:Leucine-tRNA Ligase / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D056004:Molecular Dynamics Simulation; D011789:Quantum Theory; D012984:Software
chemical_list: D001400:Azurin; D007935:Leucine-tRNA Ligase