title: Identifying Loop-Mediated Protein-Protein Interactions Using LoopFinder.
abstract: Peptides are an increasingly useful class of molecules, finding unique applications as chemical probes and potential drugs. They are particularly adept at inhibiting protein-protein interactions, which are often difficult to target using small molecules. The identification and rational design of protein-binding epitopes remains a bottleneck in the development of bioactive peptides. One fruitful strategy has been using structured scaffolds to present essential hot spot residues involved in protein-protein recognition, and this process has been greatly advanced by computational tools that can identify hot spot residues. Here we discuss LoopFinder, a program that uses structures from the Protein Data Bank to comprehensively search for protein-protein interactions that are mediated by nonhelical, nonsheet loop structures. We developed LoopFinder to identify these "hot loops" and to assist in the design of cyclic peptides that mimic these important structures. In this article, we provide all key files, outline step-by-step methods for users to conduct independent LoopFinder searches, and provide guidance on additional potential applications for the LoopFinder program.
authors.affiliation: Department of Chemistry, Tufts University, 62 Talbot Ave., Medford, MA, 02155, USA.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Siegert
authors.affiliation: Department of Chemistry, Tufts University, 62 Talbot Ave., Medford, MA, 02155, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bird
authors.affiliation: Department of Chemistry, Tufts University, 62 Talbot Ave., Medford, MA, 02155, USA. joshua.kritzer@tufts.edu.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Kritzer
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D060066:Protein Interaction Maps; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D011506:Proteins
keywords: Chemical biology; Cyclic peptides; Inhibitors; Macrocycles; Peptide design; Protein–protein interactions