Modelling the interactions between animal venom peptides and membrane proteins. (December 2017)

• Record Type: Journal Article
• Authors: Hung, Andrew; Kuyucak, Serdar; Schroeder, Christina I.; Kaas, Quentin
• Is Part Of: Neuropharmacology. Volume 127(2017)
• Page Start: 20
• Page End: 31
• Publication Date: 2017-12
• Subjects: Animal toxins -- Ion channels -- Molecular dynamics -- Molecular modelling -- Voltage-gated ion channels -- Nicotinic acetylcholine receptors; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2017.07.036
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: The active components of animal venoms are mostly peptide toxins, which typically target ion channels and receptors of both the central and peripheral nervous system, interfering with action potential conduction and/or synaptic transmission. The high degree of sequence conservation of their molecular targets makes a range of these toxins active at human receptors. The high selectivity and potency displayed by some of these toxins have prompted their use as pharmacological tools as well as drugs or drug leads. Molecular modelling has played an essential role in increasing our molecular-level understanding of the activity and specificity of animal toxins, as well as engineering them for biotechnological and pharmaceutical applications. This review focuses on the biological insights gained from computational and experimental studies of animal venom toxins interacting with membranes and ion channels. A host of recent X-ray crystallography and electron-microscopy structures of the toxin targets has contributed to a dramatic increase in the accuracy of the molecular models of toxin binding modes greatly advancing this exciting field of study. This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.' Highlights: This review highlights the use of molecular modelling in recent discoveries in the animal toxin field. The focus is on toxins acting on membranes as well as on voltage-gated ion channels and nicotinic acetylcholine receptors. The biological insights gained from using modern modelling techniques are described on a number of chosen examples. New opportunities offered by recent experimental structures for modeling toxin activity are discussed.