Assessing the energy landscape of CAPRI targets by FunHunt

Abstract

RosettaDock has repeatedly created high-resolution structures of protein complexes in the CAPRI experiment, thanks to the explicit modeling of conformational changes of the monomers at the side chain level. These models can be selected based on their energy. During the search for the lowest-energy model, RosettaDock samples a deep funnel around the native orientation, but additional funnels may appear in the energy landscape, especially in cases where backbone conformational changes occur upon binding. We have previously developed FunHunt, a Support Vector Machine-based classifier that distinguishes the energy funnels around the native orientation from other funnels in the energy landscape. Here we assess the ability of FunHunt to help in model selection in the CAPRI experiment. For all of 12 recent CAPRI targets, FunHunt clearly identifies a near-native funnel in comparison to the funnel around the lowest energy model identified by the RosettaDock global search protocol. FunHunt is also able to choose a near-native orientation among models submitted by predictor groups, demonstrating its general applicability for model selection. This suggests that FunHunt will be a valuable tool in coming CAPRI rounds for the selection of models, and for the definition of regions that need further refinement with restricted backbone flexibility. Proteins 2007. © 2007 Wiley-Liss, Inc.