Detecting protein conformational changes in interactions via scaling known structures

Abstract

Conformational changes frequently occur when proteins interact with other proteins. How to detect such changes in silico is a major problem. Existing methods for docking with conformational changes remain time-consuming, and they solve the problem only for a small portion of protein-protein complexes accurately. This work presents a more accurate method (FlexDoBi) for docking with conformational changes. FlexDoBi generates the possible conformational changes of the interface residues that transform the proteins from their unbound states to bound states. Based on the generated conformational changes, multi-dimensional scaling is performed to construct candidates for the bound structure. We develop the new energy items for determining the orientation of proteins and selecting of plausible conformational changes. Experimental results illustrate that FlexDoBi achieves better results than other methods for the same purpose. On 20 complexes, we obtained an average iRMSD of 1.55Å, which compares favorably with the average iRMSD of 1.94Å in the predictions from FiberDock. Compared with ZDOCK, our results are of 0.35Å less in average iRMSD on the medium difficulty group, and 0.81Å less on the difficulty group. © 2013 Springer-Verlag.