Computational Design of α-Conotoxins to Target Specific Nicotinic Acetylcholine Receptor Subtypes.

ABSTRACT: Nicotinic acetylcholine receptors (nAChRs) are drug targets for neurological diseases and disorders, but selective targeting of the large number of nAChR subtypes is challenging. Marine cone snail α-conotoxins are potent blockers of nAChRs and some have been engineered to achieve subtype selectivity. This engineering effort would benefit from rapid computational methods able to predict mutational energies, but current approaches typically require high-resolution experimental structures, which are not widely available for α-conotoxin complexes. Herein, five mutational energy prediction methods were benchmarked using crystallographic and mutational data on two acetylcholine binding protein/α-conotoxin systems. Molecular models were developed for six nAChR subtypes in complex with five α-cono

SUBMITTER: Wu X 

PROVIDER: S-EPMC10872529 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature