Computational allosteric ligand binding site identification on Ras proteins.
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.
Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Michael
M
McCarthy
Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Priyanka
P
Prakash
Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA alemayehu.g.abebe@uth.tmc.edu.
Alemayehu A
AA
Gorfe
D000495:Allosteric Site; D000970:Antineoplastic Agents / Q000737:chemistry*; D001665:Binding Sites; D020134:Catalytic Domain; D019295:Computational Biology; D003198:Computer Simulation; D055808:Drug Discovery; D020558:GTP Phosphohydrolases / Q000737:chemistry; D006160:Guanosine Triphosphate / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008055:Lipids / Q000737:chemistry; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D012984:Software; D018631:ras Proteins / Q000737:chemistry*
D000970:Antineoplastic Agents; D008024:Ligands; D008055:Lipids; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; D018631:ras Proteins
Ras proteins; binding site identification; molecular dynamics; probe-based simulation