title: Molecular Simulations of Disulfide-Rich Venom Peptides with Ion Channels and Membranes.
abstract: Disulfide-rich peptides isolated from the venom of arthropods and marine animals are a rich source of potent and selective modulators of ion channels. This makes these peptides valuable lead molecules for the development of new drugs to treat neurological disorders. Consequently, much effort goes into understanding their mechanism of action. This paper presents an overview of how molecular simulations have been used to study the interactions of disulfide-rich venom peptides with ion channels and membranes. The review is focused on the use of docking, molecular dynamics simulations, and free energy calculations to (i) predict the structure of peptide-channel complexes; (ii) calculate binding free energies including the effect of peptide modifications; and (iii) study the membrane-binding properties of disulfide-rich venom peptides. The review concludes with a summary and outlook.
authors.affiliation: School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6102, Australia. evelyne.deplazes@curtin.edu.au.|School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia. evelyne.deplazes@curtin.edu.au.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Deplazes
mesh_terms: D000818:Animals; D059001:Aquatic Organisms / Q000737:chemistry; D001181:Arthropods / Q000737:chemistry; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D004220:Disulfides / Q000737:chemistry*; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D014688:Venoms / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D004220:Disulfides; D007473:Ion Channels; D010455:Peptides; D014688:Venoms
keywords: free energy calculations; ion channels; molecular docking; molecular dynamics simulations; molecular modelling; structure-based drug design; venom peptides