Exploiting enzyme evolution for computational protein design
- PMID: 34544655
- DOI: 10.1016/j.tibs.2021.08.008
Exploiting enzyme evolution for computational protein design
Abstract
Recent years have seen an explosion of interest in understanding the physicochemical parameters that shape enzyme evolution, as well as substantial advances in computational enzyme design. This review discusses three areas where evolutionary information can be used as part of the design process: (i) using ancestral sequence reconstruction (ASR) to generate new starting points for enzyme design efforts; (ii) learning from how nature uses conformational dynamics in enzyme evolution to mimic this process in silico; and (iii) modular design of enzymes from smaller fragments, again mimicking the process by which nature appears to create new protein folds. Using showcase examples, we highlight the importance of incorporating evolutionary information to continue to push forward the boundaries of enzyme design studies.
Keywords: conformational dynamics; directed evolution; enhanced sampling approaches; residue coevolution; structural bioinformatics.
Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Conflict of interest statement
Declaration of interests No interests are declared.
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