Coarse-grained view of signal transduction in receptor proteins

PHYS 95

Ilya A Balabin, ilya.balabin@duke.edu, Weitao Yang, and David N. Beratan, david.beratan@duke.edu. Department of Chemistry, Duke University, Durham, NC 27708-0349
We introduce a novel metric that quantifies signal transduction properties of receptor proteins. The new metric characterizes changes in the protein structure and motion coupled to protein-ligand interactions. The metric is built upon normal mode analysis of a coarse-grained (CG) protein structure, and is therefore robust to minor structural details but capable of capturing essential conformational changes involved in signal transduction. We use the new metric to explore signal transduction mechanisms in the two G-protein coupled receptors (GPCRs) with known 3-dimensional structure, rhodopsin and the beta2-adrenergic receptor. Similarities and differences between the two receptors, along with implications for the receptor function and drug design, are described.