Rational Design of α-Conotoxin RegIIA Analogues Selectively Inhibiting the Human α3β2 Nicotinic Acetylcholine Receptor through Computational Scanning.
Molecular dynamics simulations
Mutagenesis
Structure−activity relationship
α-Conotoxin, Nicotinic acetylcholine receptor
Journal
ACS chemical neuroscience
ISSN: 1948-7193
Titre abrégé: ACS Chem Neurosci
Pays: United States
ID NLM: 101525337
Informations de publication
Date de publication:
16 09 2020
16 09 2020
Historique:
pubmed:
11
7
2020
medline:
22
6
2021
entrez:
11
7
2020
Statut:
ppublish
Résumé
Engineering the selectivity of α-conotoxins for nicotinic acetylcholine receptors (nAChRs) presents considerable complexity and challenges, as it involves the optimization of their binding affinities to multiple highly conserved nAChR subtypes. Here, we applied a computational-based scanning approach for the rational design of α-conotoxin RegIIA analogues selectively targeting the human (h) α3β2 versus hα3β4 nAChRs. Binding mode analyses suggested that several residues in loop II of RegIIA (position 9, 10, and 11) formed nonconserved interactions with residues of the β2 and β4 subunits. The molecular mechanics generalized Born surface area method was applied for
Identifiants
pubmed: 32649832
doi: 10.1021/acschemneuro.0c00293
doi:
Substances chimiques
Conotoxins
0
Nicotinic Antagonists
0
Receptors, Nicotinic
0
Acetylcholine
N9YNS0M02X
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM