Challenges in computational studies of enzyme structure, function and dynamics

Alexandra T P Carvalho; Alexandre Barrozo; Dvir Doron; Alexandra Vardi Kilshtain; Dan Thomas Major; Shina Caroline Lynn Kamerlin

doi:10.1016/j.jmgm.2014.09.003

Challenges in computational studies of enzyme structure, function and dynamics

J Mol Graph Model. 2014 Nov:54:62-79. doi: 10.1016/j.jmgm.2014.09.003. Epub 2014 Sep 28.

Authors

Alexandra T P Carvalho¹, Alexandre Barrozo¹, Dvir Doron², Alexandra Vardi Kilshtain², Dan Thomas Major³, Shina Caroline Lynn Kamerlin⁴

Affiliations

¹ Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, BMC Box 596, S-751 24 Uppsala, Sweden.
² Department of Chemistry and the Lise Meitner-Minerva Center of Computational Quantum Chemistry Bar-Ilan University, Ramat-Gan 52900, Israel.
³ Department of Chemistry and the Lise Meitner-Minerva Center of Computational Quantum Chemistry Bar-Ilan University, Ramat-Gan 52900, Israel. Electronic address: [email protected].
⁴ Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, BMC Box 596, S-751 24 Uppsala, Sweden. Electronic address: [email protected].

PMID: 25306098
DOI: 10.1016/j.jmgm.2014.09.003

Abstract

In this review we give an overview of the field of Computational enzymology. We start by describing the birth of the field, with emphasis on the work of the 2013 chemistry Nobel Laureates. We then present key features of the state-of-the-art in the field, showing what theory, accompanied by experiments, has taught us so far about enzymes. We also briefly describe computational methods, such as quantum mechanics-molecular mechanics approaches, reaction coordinate treatment, and free energy simulation approaches. We finalize by discussing open questions and challenges.

Keywords: Computational enzymology; Conformational sampling; Free energy simulations; QM/MM; Reaction coordinates.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Enzymes / chemistry*
Enzymes / metabolism*
Models, Molecular
Molecular Dynamics Simulation*

Substances

Enzymes