Investigation of the Selectivity of L-Type Voltage-Gated Calcium Channels 1.3 for Pyrimidine-2,4,6-Triones Derivatives Based on Molecular Dynamics Simulation.

ABSTRACT: Human Ca_v1.3 (hCa_v1.3) is of great interest as a potential target for Parkinson's disease. However, common medications like dihydropyridines (DHPs), a kind of classic calcium channel blocker, have poor selectivity to hCa_v1.3 in clinical treatment, mainly due to being implicated in cardiovascular side-effects mediated by human Ca_v1.2 (hCa_v1.2). Recently, pyrimidine-2,4,6-triones (PYTs) have received extensive attention as prominent selective inhibitors to hCa_v1.3. In this study, we describe the selectivity mechanism of PYTs for hCa_v1.2 and hCa_v1.3 based on molecular dynamic simulation methods. Our results reveal that the van der Waals (vdW) interaction was the most important force affecting selectivity.

SUBMITTER: Ye Q 

PROVIDER: S-EPMC7699898 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature