Blockade of Human ?7 Nicotinic Acetylcholine Receptor by ?-Conotoxin ImI Dendrimer: Insight from Computational Simulations.

ABSTRACT: Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that are involved in fast synaptic transmission and mediated physiological activities in the nervous system. ?-Conotoxin ImI exhibits subtype-specific blockade towards homomeric ?7 and ?9 receptors. In this study, we established a method to build a 2×ImI-dendrimer/h (human) ?7 nAChR model, and based on this model, we systematically investigated the molecular interactions between the 2×ImI-dendrimer and h?7 nAChR. Our results suggest that the 2×ImI-dendrimer possessed much stronger potency towards h?7 nAChR than the ?-ImI monomer and demonstrated that the linker between ?-ImI contributed to the potency of the 2×ImI-dendrimer by forming a stable hydrogen-bond network with h?7 nAChR. Overall, this study provides novel insights into the binding mechanism of ?-ImI dendrimer to h?7 nAChR, and the methodology reported here opens an avenue for the design of more selective dendrimers with potential usage as drug/gene carriers, macromolecular drugs, and molecular probes.

SUBMITTER: Xu X 

PROVIDER: S-EPMC6563025 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature