Rosetta FlexPepDock web server--high resolution modeling of peptide-protein interactions

Abstract

Peptide-protein interactions are among the most prevalent and important interactions in the cell, but a large fraction of those interactions lack detailed structural characterization. The Rosetta FlexPepDock web server (http://flexpepdock.furmanlab.cs.huji.ac.il/) provides an interface to a high-resolution peptide docking (refinement) protocol for the modeling of peptide-protein complexes, implemented within the Rosetta framework. Given a protein receptor structure and an approximate, possibly inaccurate model of the peptide within the receptor binding site, the FlexPepDock server refines the peptide to high resolution, allowing full flexibility to the peptide backbone and to all side chains. This protocol was extensively tested and benchmarked on a wide array of non-redundant peptide-protein complexes, and was proven effective when applied to peptide starting conformations within 5.5 Å backbone root mean square deviation from the native conformation. FlexPepDock has been applied to several systems that are mediated and regulated by peptide-protein interactions. This easy to use and general web server interface allows non-expert users to accurately model their specific peptide-protein interaction of interest.

Figure 1.

Results provided for an example peptide docking run. (A) Graphical representation of the top 10 models (superimposed), as well as more detailed figures of the top 5 models (second row). (B) Plot of RMSD (x-axis) vs score (y-axis) of all models created by the simulation run. Bottom panel: The top 10 models (PDB format coordinates), as well as a score file can be downloaded via the provided links. This example is based on a 4.9A bb-RMSD starting conformation and is taken from line 6 in Table 1.