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Only a few PAAs have the binding specificity on calcium channels, for example, NNC 55\u20100396. Here, we created the homology models of human Ca<jats:sub>v<\/jats:sub>3.2, Ca<jats:sub>v<\/jats:sub>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\u20100396 had a unique binding pattern on domain II specifically. The subsequent molecular dynamics (MD) simulations identified that Ca<jats:sub>v<\/jats:sub>3.1, Ca<jats:sub>v<\/jats:sub>3.2, and Ca<jats:sub>v<\/jats:sub>3.3 share domain II when Ca<jats:sup>2+<\/jats:sup> appearing in the neighbor region of selective filters (SFs). Moreover, free\u2010energy perturbation analysis suggests single mutation of lysine at P\u2010loop domain III, or threonine at the P\u2010loop domain II largely reduced the total amount of hydration\u2010free energy in the system. All these findings suggest that P\u2010loop and segment six domain II in the T\u2010type calcium channels (TCCs) are crucial for attracting the PAAs with specificity as the antagonist.<\/jats:p>","DOI":"10.1002\/prp2.783","type":"journal-article","created":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T16:54:22Z","timestamp":1620924862000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Seeking the exclusive binding region of phenylalkylamine derivatives on human T\u2010type calcium channels via homology modeling and molecular dynamics simulation approach"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6815-6568","authenticated-orcid":false,"given":"You","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Physics and Computer Science Xavier University of Louisiana New Orleans LA USA"},{"name":"Bioinformatics Core of Xavier NIH RCMI Center of Cancer 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