title: PepCrawler: a fast RRT-based algorithm for high-resolution refinement and binding affinity estimation of peptide inhibitors.
abstract: BACKGROUND
  Design of protein-protein interaction (PPI) inhibitors is a key challenge in structural bioinformatics and computer-aided drug design. Peptides, which partially mimic the interface area of one of the interacting proteins, are natural candidates to form protein-peptide complexes competing with the original PPI. The prediction of such complexes is especially challenging due to the high flexibility of peptide conformations.
  
  
  RESULTS
  In this article, we present PepCrawler, a new tool for deriving binding peptides from protein-protein complexes and prediction of peptide-protein complexes, by performing high-resolution docking refinement and estimation of binding affinity. By using a fast path planning approach, PepCrawler rapidly generates large amounts of flexible peptide conformations, allowing backbone and side chain flexibility. A newly introduced binding energy funnel 'steepness score' was applied for the evaluation of the protein-peptide complexes binding affinity. PepCrawler simulations predicted high binding affinity for native protein-peptide complexes benchmark and low affinity for low-energy decoy complexes. In three cases, where wet lab data are available, the PepCrawler predictions were consistent with the data. Comparing to other state of the art flexible peptide-protein structure prediction algorithms, our algorithm is very fast, and takes only minutes to run on a single PC.
  
  
  BACKGROUND
  http://bioinfo3d.cs.tau.ac.il/PepCrawler/
  
  
  BACKGROUND
  eladdons@tau.ac.il; wolfson@tau.ac.il.
authors: Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel. eladdons@tau.ac.il
authors: Elad
authors: E
authors: Donsky
authors: Haim J
authors: HJ
authors: Wolfson
mesh_terms: D000465:Algorithms; D015195:Drug Design; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D025941:Protein Interaction Mapping / Q000379:methods*
chemical_list: D046912:Multiprotein Complexes; D010455:Peptides