Modeling Peptide-Protein Interactions pp 255-277

Part of the Methods in Molecular Biology book series (MIMB, volume 1561) | Cite as

Identifying Loop-Mediated Protein–Protein Interactions Using LoopFinder

  • Timothy R. Siegert
  • Michael Bird
  • Joshua A. Kritzer
Protocol

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.

Key words

Protein–protein interactions Macrocycles Cyclic peptides Peptide design Inhibitors Chemical biology 

Supplementary material

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Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  • Timothy R. Siegert
    • 1
  • Michael Bird
    • 1
  • Joshua A. Kritzer
    • 1
  1. 1.Department of ChemistryTufts UniversityMedfordUSA

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