title: In silico strategies toward enzyme function and dynamics.
abstract: Enzymes are outstanding biocatalysts involved in a plethora of chemical reactions occurring in the cell. Despite their incommensurable importance, a comprehensive understanding of enzyme catalysis is still missing. This task becomes more laborious given the unavoidability of including the inherent dynamic nature of enzymes into that description. As such, it is essential to ascertain the nature and contribution of enzyme conformational changes to catalysis and to evaluate the adequacy of the proposal associating protein internal motions to the rate enhancement achieved. Dynamic events in enzymes span a wide range of time- and length-scales which have led to a surge in multiscale methodologies targeting enzyme function and dynamics. Computational strategies assume a preponderant role in such studies by allowing the atomic detail investigation of the fundamental mechanisms of enzyme catalysis thus surpassing what is achievable through experiments. While high-accuracy quantum mechanical methods are indicated to uncover the details of the chemical reaction occurring at the active site, molecular mechanical force fields and molecular dynamics approaches provide powerful means to access the conformational energy landscape accessible to enzymes. This review outlines some of the most important in silico methodologies in this area, highlighting examples of problems tackled and the insights obtained.
authors.affiliation: Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon. Lisbon, Portugal.
authors.forename: Sílvia G
authors.initials: SG
authors.lastname: Estácio
mesh_terms: D003198:Computer Simulation; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D011789:Quantum Theory
chemical_list: D004798:Enzymes