LoopFinder is an online resource for investigating loop-mediated protein-protein interactions, and for developing starting points for inhibitor design. It was produced and developed by the Kritzer Laboratory, Dept. of Chemistry, Tufts University. This page serves as an introduction to the LoopFinder tool and its applications.
Inhibiting protein-protein interactions (PPIs) with synthetic molecules remains a frontier of chemical biology. Many PPIs have been successfully targeted by mimicking α-helices and other secondary structures, but most PPIs are mediated by nonhelical, nonstrand peptide loops. We sought to comprehensively identify these loop-mediated PPIs by developing a customizable program, called LoopFinder, that can systematically find and analyze loop-mediated PPIs within the Protein Data Bank. In 2014, we reported the comprehensive analysis of a set of 25,005 interface loops, revealing common structural motifs and unique features that distinguish loop-mediated PPIs from other PPIs. Loops with multiple residues that were predicted to be critical for their associated PPI were defined as ‘hot loops’, named in analogy to PPI ‘hot spots’. Hot loops have favorable properties for mimicry using synthetic molecules. The hot loops and their binding partners represent new and promising PPIs for the development of macrocycle and constrained peptide inhibitors.
LoopFinder has now been released as an online tool for finding and analyzing PPIs within the Protein Data Bank. The primary application of this tool has been to identify new targets and starting points for macrocycle design. However, it is readily extended to investigate larger loops or entire protein domains, both for understanding basic biology and for developing small-molecule or protein mimics.
What you can do with LoopFinder:
- To view the original LoopFinder article, see Comprehensive Analysis of Loops at Protein-Protein Interfaces for Macrocycle Design by Gavenonis, Sheneman, Siegert, Eshelman, and Kritzer. Nat Chem Biol, 10, 716-722.
- To view the followup LoopFinder article, which presented refined criteria for loop definitions and structural clusters of common loops at PPI interfaces, see Analysis of Loops that Mediate Protein-Protein Interactions and Translation into Sub-Micromolar Inhibitors. by Siegert, Bird, Makwana and Kritzer. J Am Chem Soc, 138, 12876-12884.
- Additional resources and instructions for implementing LoopFinder can be found at: Identifying Loop-Mediated Protein-Protein Interactions Using LoopFinder by Siegert, Bird, and Kritzer. Meth Mol Biol, 1561, 255-277.
- You can use LoopFinder to identify hot loops in a single PDB file of interest.
- You can also browse or query our databases of loop-mediated PPIs. We have databases corresponding to small loops ideal for macrocycle design, and larger loops that encompass antibody loops and other recognition domains.
- You can also explore our new tools for grafting hot loops onto well-folded protein scaffolds.