Computational studies on cholinesterases: Strengthening our understanding of the integration of structure, dynamics and function

Joel L Sussman; Israel Silman

doi:10.1016/j.neuropharm.2020.108265

Computational studies on cholinesterases: Strengthening our understanding of the integration of structure, dynamics and function

Neuropharmacology. 2020 Nov 15:179:108265. doi: 10.1016/j.neuropharm.2020.108265. Epub 2020 Aug 11.

Authors

Joel L Sussman¹, Israel Silman²

Affiliations

¹ Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel. Electronic address: Joel.Sussman@weizmann.ac.il.
² Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.

PMID: 32795461
DOI: 10.1016/j.neuropharm.2020.108265

Abstract

Computational approaches have proved valuable in elucidating structure/function relationships in the cholinesterases in the context of their unusual three-dimensional structure. In this review we survey several recent studies that have enhanced our understanding of how these enzymes function, and have utilized computational approaches both to modulate their activity and to improve the design of lead compounds for their inhibition. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:Neuropharmacology:2.

Keywords: Acetylcholinesterase; Butyrylcholinesterase; Docking; Molecular dynamics; PROSS; Structure reassessment.

Publication types

Review

MeSH terms

Animals
Binding Sites / physiology
Cholinesterases / chemistry*
Cholinesterases / physiology*
Crystallography, X-Ray / methods
Humans
Molecular Docking Simulation / methods*
Molecular Dynamics Simulation*
Protein Structure, Secondary
Protein Structure, Tertiary

Substances

Cholinesterases