title: Challenges in computational studies of enzyme structure, function and dynamics.
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.
authors.affiliation: Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, BMC Box 596, S-751 24 Uppsala, Sweden.
authors.forename: Alexandra T P
authors.initials: AT
authors.lastname: Carvalho
authors.affiliation: Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, BMC Box 596, S-751 24 Uppsala, Sweden.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Barrozo
authors.affiliation: Department of Chemistry and the Lise Meitner-Minerva Center of Computational Quantum Chemistry Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: Dvir
authors.initials: D
authors.lastname: Doron
authors.affiliation: Department of Chemistry and the Lise Meitner-Minerva Center of Computational Quantum Chemistry Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: Alexandra Vardi
authors.initials: AV
authors.lastname: Kilshtain
authors.affiliation: Department of Chemistry and the Lise Meitner-Minerva Center of Computational Quantum Chemistry Bar-Ilan University, Ramat-Gan 52900, Israel. Electronic address: majort@biu.ac.il.
authors.forename: Dan Thomas
authors.initials: DT
authors.lastname: Major
authors.affiliation: Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, BMC Box 596, S-751 24 Uppsala, Sweden. Electronic address: kamerlin@icm.uu.se.
authors.forename: Shina Caroline Lynn
authors.initials: SC
authors.lastname: Kamerlin
mesh_terms: D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation
chemical_list: D004798:Enzymes
keywords: Computational enzymology; Conformational sampling; Free energy simulations; QM/MM; Reaction coordinates