The role of conserved waters in conformational transitions of Q61H K-ras.

ABSTRACT: To investigate the stability and functional role of long-residence water molecules in the Q61H variant of the signaling protein K-ras, we analyzed all available Ras crystal structures and conformers derived from a series of independent explicit solvent molecular dynamics (MD) simulations totaling 1.76 µs. We show that the protein samples a different region of phase space in the presence and absence of several crystallographically conserved and buried water molecules. The dynamics of these waters is coupled with the local as well as the global motions of the protein, in contrast to less buried waters whose exchange with bulk is only loosely coupled with the motion of loops in their vicinity. Aided by two novel reaction coordinates involving the distance (d) between the C(α) atoms of G60 at

SUBMITTER: Prakash P 

PROVIDER: S-EPMC3280954 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature