Computational modeling of allosteric communication reveals organizing principles of mutation-induced signaling in ABL and EGFR kinases.

ABSTRACT: The emerging structural information about allosteric kinase complexes and the growing number of allosteric inhibitors call for a systematic strategy to delineate and classify mechanisms of allosteric regulation and long-range communication that control kinase activity. In this work, we have investigated mechanistic aspects of long-range communications in ABL and EGFR kinases based on the results of multiscale simulations of regulatory complexes and computational modeling of signal propagation in proteins. These approaches have been systematically employed to elucidate organizing molecular principles of allosteric signaling in the ABL and EGFR multi-domain regulatory complexes and analyze allosteric signatures of the gate-keeper cancer mutations. We have presented evidence that mechanisms o

SUBMITTER: Dixit A 

PROVIDER: S-EPMC3188506 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature