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 proteinligands and of the protein itself, showing important features of theirdynamic properties. Essential dynamics analysis of 300 ps of full solventmolecular dynamics simulations revealed differences in structure anddynamics between GDP- and GTP-bound forms of H-ras-p21. Regions in theprotein which exhibited a structural shift correspond to the switch regionsdescribed previously. Differences in dynamics between H-ras-p21 GDP andH-ras-p21 GTP may be related to interactions of ras with GAP and itsreceptor and effector. Molecular dynamics of free GDP (in the absence ofprotein) were performed in water for 2 ns and analysed using essentialdynamics. The conformations of GDP and GTP when bound to the protein werecompared with free GDP, revealing that the ligands bind to the protein inan energetically unfavourable conformation. GDP and GTP molecules fromvarious other protein crystal structures were also analysed. These ligandsadopt similar conformations to those seen in H-ras-p21.