The Trials and Tribulations of Structure Assisted Design of K_Ca Channel Activators.

ABSTRACT: Calcium-activated K⁺ channels constitute attractive targets for the treatment of neurological and cardiovascular diseases. To explain why certain 2-aminobenzothiazole/oxazole-type K_Ca activators (SKAs) are K_Ca3.1 selective we previously generated homology models of the C-terminal calmodulin-binding domain (CaM-BD) of K_Ca3.1 and K_Ca2.3 in complex with CaM using Rosetta modeling software. We here attempted to employ this atomistic level understanding of K_Ca activator binding to switch selectivity around and design K_Ca2.2 selective activators as potential anticonvulsants. In this structure-based drug design approach we used RosettaLigand docking and carefully compared the binding poses of various SKA compounds in the

SUBMITTER: Shim H 

PROVIDER: S-EPMC6764326 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature