1. A simple contact mapping algorithm for identifying potential peptide mimetics in protein-protein interaction partners
- Author
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Alex Krall, Jonathan Brunn, Spandana Kankanala, and Michael H. Peters
- Subjects
Peptide ,Interatomic potential ,Computational biology ,protein–protein interactions ,Biology ,Biochemistry ,Force field (chemistry) ,static mapping ,Protein–protein interaction ,Proto-Oncogene Proteins c-myc ,Structural Biology ,Biomimetic Materials ,Mapping algorithm ,Protein Interaction Maps ,Molecular Biology ,chemistry.chemical_classification ,Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ,Articles ,Combinatorial chemistry ,HIV Envelope Protein gp41 ,Protein Structure, Tertiary ,ErbB Receptors ,Repressor Proteins ,chemistry ,Drug development ,Target protein ,Biomimetics ,Peptides ,peptide mimetics ,Hydrophobic and Hydrophilic Interactions ,Algorithms - Abstract
A simple, static contact mapping algorithm has been developed as a first step at identifying potential peptide biomimetics from protein interaction partner structure files. This rapid and simple mapping algorithm, “OpenContact” provides screened or parsed protein interaction files based on specified criteria for interatomic separation distances and interatomic potential interactions. The algorithm, which uses all-atom Amber03 force field models, was blindly tested on several unrelated cases from the literature where potential peptide mimetics have been experimentally developed to varying degrees of success. In all cases, the screening algorithm efficiently predicted proposed or potential peptide biomimetics, or close variations thereof, and provided complete atom-atom interaction data necessary for further detailed analysis and drug development. In addition, we used the static parsing/mapping method to develop a peptide mimetic to the cancer protein target, epidermal growth factor receptor. In this case, secondary, loop structure for the peptide was indicated from the intra-protein mapping, and the peptide was subsequently synthesized and shown to exhibit successful binding to the target protein. The case studies, which all involved experimental peptide drug advancement, illustrate many of the challenges associated with the development of peptide biomimetics, in general. Proteins 2014; 82:2253–2262. © 2014 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.
- Published
- 2014