Ras conformational switching: simulating nucleotide-dependent conformational transitions with accelerated molecular dynamics.

ABSTRACT: Ras mediates signaling pathways controlling cell proliferation and development by cycling between GTP- and GDP-bound active and inactive conformational states. Understanding the complete reaction path of this conformational change and its intermediary structures is critical to understanding Ras signaling. We characterize nucleotide-dependent conformational transition using multiple-barrier-crossing accelerated molecular dynamics (aMD) simulations. These transitions, achieved for the first time for wild-type Ras, are impossible to observe with classical molecular dynamics (cMD) simulations due to the large energetic barrier between end states. Mapping the reaction path onto a conformer plot describing the distribution of the crystallographic structures enabled identification of highly popul

SUBMITTER: Grant BJ 

PROVIDER: S-EPMC2651530 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature