A number of computational techniques have been proposed to expedite the process of allosteric ligand binding site identification in inherently flexible and hence challenging drug targets. Some of these techniques have been instrumental in the discovery of allosteric ligand binding sites on Ras proteins, a group of elusive anticancer drug targets. This review provides an overview of these techniques and their application to Ras proteins. A summary of molecular docking and binding site identification is provided first, followed by a more detailed discussion of two specific techniques for binding site identification in ensembles of Ras conformations generated by molecular simulations.
Keywords: Ras proteins; binding site identification; molecular dynamics; probe-based simulation.
© The Author 2015. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.