Mapping the conformational transition in Src activation by cumulating the information from multiple molecular dynamics trajectories.

ABSTRACT: The Src-family kinases are allosteric enzymes that play a key role in the regulation of cell growth and proliferation. In response to cellular signals, they undergo large conformational changes to switch between distinct inactive and active states. A computational strategy for characterizing the conformational transition pathway is presented to bridge the inactive and active states of the catalytic domain of Hck. The information from a large number (78) of independent all-atom molecular dynamics trajectories with explicit solvent is combined together to assemble a connectivity map of the conformational transition. Two intermediate states along the activation pathways are identified, and their structural features are characterized. A coarse free-energy landscape is built in terms of the col

SUBMITTER: Yang S 

PROVIDER: S-EPMC2656156 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature