The QM/MM Method. An Overview

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Internet Electronic Journal of Molecular Design


The paper presents an overview of the development of the QM/MM method and its application to the study of enzyme reactivity. Different approaches for the treatment of QM/MM boundary (link-atom, LSCF, pseudoatoms) are review and their strengths and weaknesses are discussed. The QM/MM Hamiltonian is briefly presented, its terms are defined and discussed, and the latest developments of the QM/MM method are presented. Finally, many of the applications of the QM/MM method over the last decade are briefly reviewed and few of the most recent results are discussed (e.g. opsin shift in bacteriorhodopsin, tunneling dynamics in liver alcohol dehydrogenase). The QM/MM method proved to be one of the most successful theoretical approach for studying biomolecular systems, and its future development will make it the most sophisticated computational tool for the investigation of enzyme reactivity. In addition, the newly developed linear scaling QM algorithms and the composite Hamiltonian approach are among the latest developments that promise to make the QM/MM method a very efficient and versatile computational tool for biochemistry.