Abstract:Ras-positive cancer constitutes a major challenge for medical treatment. Hot spot residues Gly12, Gly13 and Gln61 constitute the majority of oncogenic mutations which are associated with detrimental clinical prognosis. Here we present a two-step mechanism of GTP hydrolysis of the wild type Ras.GAP complex using QM/MM free energy calculations with the finite-temperature string method. We found that the deprotonation of the catalytic water takes place via the Gln61 as a transient Brønsted base. We obtained react… Show more
Set email alert for when this publication receives citations?
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.