Monte Carlo-energy minimization of correolide in the Kv1.3 channel: possible role of potassium ion in ligand-receptor interactions.

ABSTRACT:

Background

Correolide, a nortriterpene isolated from the Costa Rican tree Spachea correa, is a novel immunosuppressant, which blocks Kv1.3 channels in human T lymphocytes. Earlier mutational studies suggest that correolide binds in the channel pore. Correolide has several nucleophilic groups, but the pore-lining helices in Kv1.3 are predominantly hydrophobic raising questions about the nature of correolide-channel interactions.

Results

We employed the method of Monte Carlo (MC) with energy minimization to search for optimal complexes of correolide in Kv1.2-based models of the open Kv1.3 with potassium binding sites 2/4 or 1/3/5 loaded with K+ ions. The energy was MC-minimized from many randomly generated starting positions and orientations of the ligand. In all the predicted

SUBMITTER: Bruhova I 

PROVIDER: S-EPMC1796882 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature