Molecular dynamics simulations reveal ligand-controlled positioning of a peripheral protein complex in membranes.

ABSTRACT: Bryostatin is in clinical trials for Alzheimer's disease, cancer, and HIV/AIDS eradication. It binds to protein kinase C competitively with diacylglycerol, the endogenous protein kinase C regulator, and plant-derived phorbol esters, but each ligand induces different activities. Determination of the structural origin for these differing activities by X-ray analysis has not succeeded due to difficulties in co-crystallizing protein kinase C with relevant ligands. More importantly, static, crystal-lattice bound complexes do not address the influence of the membrane on the structure and dynamics of membrane-associated proteins. To address this general problem, we performed long-timescale (400-500 µs aggregate) all-atom molecular dynamics simulations of protein kinase C-ligand-membrane complexes

SUBMITTER: Ryckbosch SM 

PROVIDER: S-EPMC5431895 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature