Conformations and binding pockets of HRas and its guanine nucleotide exchange factors complexes in the guanosine triphosphate exchange process.

ABSTRACT: The human Son of Sevenless (SOS) activates the signal-transduction protein Ras by forming the complex SOS·Ras and accelerating the guanosine triphosphate (GTP) exchange in Ras. Inhibition of SOS·Ras could regulate the function of Ras in cells and has emerged as an effective strategy for battling Ras related cancers. A key factor to the success of this approach is to understand the conformational change of Ras during the GTP exchange process. In this study, we perform an extensive molecular dynamics simulation to characterize the specific conformations of Ras without and with guanine nucleotide exchange factors (GEFs) of SOS, especially for the substates of State 1 of HRasGTP∙Mg²⁺ . The potent binding pockets on the surfaces of the RasGDP∙Mg²⁺ , the S1.1 and S1.2 subst

SUBMITTER: Xiong Y 

PROVIDER: S-EPMC9191747 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature