Molecular Dynamics-Derived Pharmacophore Model Explaining the Nonselective Aspect of K_V10.1 Pore Blockers.

ABSTRACT: The K_V10.1 voltage-gated potassium channel is highly expressed in 70% of tumors, and thus represents a promising target for anticancer drug discovery. However, only a few ligands are known to inhibit K_V10.1, and almost all also inhibit the very similar cardiac hERG channel, which can lead to undesirable side-effects. In the absence of the structure of the K_V10.1-inhibitor complex, there remains the need for new strategies to identify selective K_V10.1 inhibitors and to understand the binding modes of the known K_V10.1 inhibitors. To investigate these binding modes in the central cavity of K_V10.1, a unique approach was used that allows derivation and analysis of ligand-protein interactions from molecular dynamics trajectories t

SUBMITTER: Toplak Z 

PROVIDER: S-EPMC8396485 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature