An in silico study of the molecular basis of B-RAF activation and conformational stability.

ABSTRACT:

Background

B-RAF kinase plays an important role both in tumour induction and maintenance in several cancers and it is an attractive new drug target. However, the structural basis of the B-RAF activation is still not well understood.

Results

In this study we suggest a novel molecular basis of B-RAF activation based on molecular dynamics (MD) simulations of B-RAFWT and the B-RAFV600E, B-RAFK601E and B-RAFD594V mutants. A strong hydrogen bond network was identified in B-RAFWT in which the interactions between Lys601 and the well known catalytic residues Lys483, Glu501 and Asp594 play an important role. It was found that several mutations, which directly or indirectly destabilized the interactions between these residues within this network, contributed to the changes in B-RAF ac

SUBMITTER: Fratev FF 

PROVIDER: S-EPMC2731097 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature