Paper Citing NAMD - Abstract
Mironov, Vladimir A.; Khrenova, Maria G.; Lychko, Leonora A.; Nemukhin, Alexander V.
Computational characterization of the chemical step in the GTP hydrolysis by Ras-GAP for the wild-type and G13V mutated Ras
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 83:1046-1053, JUN 2015
The free energy profiles for the chemical reaction of the guanosine triphosphate hydrolysis GTP+H2O GDP+Pi by Ras-GAP for the wild-type and G13V mutated Ras were computed by using molecular dynamics protocols with the QM(ab initio)/MM potentials. The results are consistent with the recent measurements of reaction kinetics in Ras-GAP showing about two-order reduction of the rate constant upon G13V mutation in Ras: the computed activation barrier on the free energy profile is increased by 3 kcal/mol upon the G13V replacement. The major reason for a higher energy barrier is a shift of the arginine finger (R789 from GAP) from the favorable position in the active site. The results of simulations provide support for the mechanism of the reference reaction according to which the Q61 side chain directly participates in chemical transformations at the proton transfer stage. Proteins 2015; 83:1046-1053. (c) 2015 Wiley Periodicals, Inc.
