Ligand Docking to Intermediate and Close-To-Bound Conformers Generated by an Elastic Network Model Based Algorithm for Highly Flexible Proteins.

ABSTRACT: Incorporating receptor flexibility in small ligand-protein docking still poses a challenge for proteins undergoing large conformational changes. In the absence of bound structures, sampling conformers that are accessible by apo state may facilitate docking and drug design studies. For this aim, we developed an unbiased conformational search algorithm, by integrating global modes from elastic network model, clustering and energy minimization with implicit solvation. Our dataset consists of five diverse proteins with apo to complex RMSDs 4.7-15 Å. Applying this iterative algorithm on apo structures, conformers close to the bound-state (RMSD 1.4-3.8 Å), as well as the intermediate states were generated. Dockings to a sequence of conformers consisting of a closed structure and its "parents" up

SUBMITTER: Kurkcuoglu Z 

PROVIDER: S-EPMC4922591 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature