Seeking the exclusive binding region of phenylalkylamine derivatives on human T-type calcium channels via homology modeling and molecular dynamics simulation approach.

ABSTRACT: Pharmaceutical features of phenylalkylamine derivatives (PAAs) binding to calcium channels have been studied extensively in the past decades. Only a few PAAs have the binding specificity on calcium channels, for example, NNC 55-0396. Here, we created the homology models of human Ca_v 3.2, Ca_v 3.3 and use them as a receptor on the rigid docking tests. The nonspecific calcium channel blocker mibefradil showed inconsistent docking preference across four domains; however, NNC 55-0396 had a unique binding pattern on domain II specifically. The subsequent molecular dynamics (MD) simulations identified that Ca_v 3.1, Ca_v 3.2, and Ca_v 3.3 share domain II when Ca²⁺ appearing in the neighbor region of selective filters (SFs). Moreover,

SUBMITTER: Lu Y 

PROVIDER: S-EPMC8118199 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature