Biological Applications of Hybrid Quantum Mechanics/Molecular Mechanics Calculation

Jiyoung Kang,Yohsuke Hagiwara,Masaru Tateno

doi:10.1155/2012/236157

Jiyoung Kang, Yohsuke Hagiwara + Show 1 more

Open Access

https://doi.org/10.1155/2012/236157

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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 tRNALeu, 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.

Highlights

Ab initio quantum mechanical (QM) calculation is an important tool to investigate functional mechanisms of biological macromolecules based on their three-dimensional and electronic structures
Disadvantages of the subtractive schemes are the following: (1) force fields are required for describing the QM region which often includes ligands and intermediate structures of enzymatic reactions; in general, reliable force fields of the molecules are not prepared, and additional QM calculations should be carried out for the parameterization every time a new system is studied; (2) the electrostatic interactions between the QM and MM regions are described at molecular mechanics level; that is, the interactions are calculated by the Coulomb interactions between fixed atomic charges in the QM and MM regions
Overhead costs of the UNIX shell which arise from treating huge amount of information such as number of atoms of a solvated system of the biological system were avoided using C programs and modifications of the AMBER and GAMESS source code

Summary

Introduction

Ab initio quantum mechanical (QM) calculation is an important tool to investigate functional mechanisms of biological macromolecules based on their three-dimensional and electronic structures. Disadvantages of the subtractive schemes are the following: (1) force fields are required for describing the QM region which often includes ligands and intermediate structures of enzymatic reactions; in general, reliable force fields of the molecules are not prepared, and additional QM calculations should be carried out for the parameterization every time a new system is studied; (2) the electrostatic interactions between the QM and MM regions are described at molecular mechanics level; that is, the interactions are calculated by the Coulomb interactions between fixed atomic charges in the QM and MM regions Such description cannot represent polarization of the QM region induced by environment surrounding the QM region. The issues on the treatments of electrostatic interactions between QM and MM regions are important in the calculation efficiency and have been discussed previously [50, 51]

Investigation of Environmental Effects on Electronic Structure of QM Region

Findings

Conclusions