COMPARISON OF RAS-P21 BOUND TO GDP AND GTP - DIFFERENCES IN PROTEIN AND LIGAND DYNAMICS

This paper documents the first essential dynamics analysis of ras prot ein ligands and of the protein itself, showing important features of t heir dynamic properties. Essential dynamics analysis of 300 ps of full solvent molecular dynamics simulations revealed differences in struct ure and dynamics between GDP- and GTP-bound forms of H-ras-p21. Region s in the protein which exhibited a structural shift correspond to the switch regions described previously. Differences in dynamics between H -ras-p21 GDP and H-ras-p21 GTP may be related to interactions of ras w ith GAP and its receptor and effector. Molecular dynamics of free GDP (in the absence of protein) were performed in water for 2 ns and analy sed using essential dynamics. The conformations of GDP and GTP when bo und to the protein were compared with free GDP, revealing that the lig ands bind to the protein in an energetically unfavourable conformation . GDP and GTP molecules from various other protein crystal structures were also analysed. These ligands adopt similar conformations to those seen in H-ras-p21.