Steered molecular dynamics simulations reveal the likelier dissociation pathway of imatinib from its targeting kinases c-Kit and Abl.

ABSTRACT: Development of small molecular kinase inhibitors has recently been the central focus in drug discovery. And type II kinase inhibitors that target inactive conformation of kinases have attracted particular attention since their potency and selectivity are thought to be easier to achieve compared with their counterpart type I inhibitors that target active conformation of kinases. Although mechanisms underlying the interactions between type II inhibitors and their targeting kinases have been widely studied, there are still some challenging problems, for example, how type II inhibitors associate with or dissociate from their targeting kinases. In this investigation, steered molecular dynamics simulations have been carried out to explore the possible dissociation pathways of typical type II inh

SUBMITTER: Yang LJ 

PROVIDER: S-EPMC2795779 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature