Distinct dynamics and interaction patterns in H- and K-Ras oncogenic P-loop mutants.

ABSTRACT: Despite years of study, the structural or dynamical basis for the differential reactivity and oncogenicity of Ras isoforms and mutants remains unclear. In this study, we investigated the effects of amino acid variations on the structure and dynamics of wild type and oncogenic mutants G12D, G12V, and G13D of H- and K-Ras proteins. Based on data from µs-scale molecular dynamics simulations, we show that the overall structure of the proteins remains similar but there are important differences in dynamics and interaction networks. We identified differences in residue interaction patterns around the canonical switch and distal loop regions, and persistent sodium ion binding near the GTP particularly in the G13D mutants. Our results also suggest that different Ras variants have distinct local st

SUBMITTER: Sayyed-Ahmad A 

PROVIDER: S-EPMC5568977 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature