A molecular dynamics study of Hras-GTP and GDP complexes: The properties of water molecules around guanine nucleotide

We study the structures of Hras-GTP and Hras-GDP complexes in water in order to investigate the mechanism of hydrolysis of GTP in the Hras-GTP complex. Understanding of the mechanism of hydrolysis of GTP in the Hras-GTP complex plays a key role in overcoming the human cancer. We performed molecular dynamics (MD) simulations of Hras-GTP complex and Hras-GDP complex in water using AMBER03 parameters and our calculated parameters around Mg2+. Using the trajectories of the MD simulations, we calculated the radial distribution functions of water molecules around the phosphorus atoms in guanine nucleotide in each complex. We also calculated the radius of the first hydration sphere, the averaged number of water molecules in the first hydration sphere, and the distribution of duration time of water molecules in the first hydration sphere. We also calculated the distribution of water molecules with respect to the angle around the PG in GTP and PB in GDP. It is suggested that the hydrolysis is triggered by water molecules attacking γ–phosphate from the direction rotated 35° to the O1B from the axis defined by PG and O3B.