A study of the molecular mechanism of binding kinetics and long residence times of human CCR5 receptor small molecule allosteric ligands.

ABSTRACT:

Background and purpose

The human CCR5 receptor is a co-receptor for HIV-1 infection and a target for anti-viral therapy. A greater understanding of the binding kinetics of small molecule allosteric ligand interactions with CCR5 will lead to a better understanding of the binding process and may help discover new molecules that avoid resistance.

Experimental approach

Using [(3) H] maraviroc as a radioligand, a number of different binding protocols were employed in conjunction with simulations to determine rate constants, kinetic mechanism and mutant kinetic fingerprints for wild-type and mutant human CCR5 with maraviroc, aplaviroc and vicriviroc.

Key results

Kinetic characterization of maraviroc binding to the wild-type CCR5 was consistent with a two-step kinetic mechan

SUBMITTER: Swinney DC 

PROVIDER: S-EPMC4105926 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature