Binding of an RNA pol II Ligand to the WW Domain of Pin1 Using Molecular Dynamics Docking Simulations

A novel docking protocol using a long, all atom molecular dynamics (MD) simulation, in an explicit solvent medium, without using any distance constraints is presented. This MD docking protocol is able to dock ligands, based on the C-terminal domain (CTD) of RNA polymerase II, into the tryptophan-tryptophan (WW) domain of Pin1. In this docking process, a significant loop-bending event occurs in order to encircle the ligand into its solvent exposed binding site, which cannot be simulated using current protocols. The simulations were validated structurally and energetically against an X-ray structure to confirm correct sampling of conformational space. Based on these simulations, and justification of the starting structure as a valid intermediate structure, a potential molecular basis for binding was predicted as well as confirming the key residues involved in the formation of the final strong and stable Pin1 WW domain-ligand complex.