A simple contact mapping algorithm for identifying potential peptide mimetics in protein-protein interaction partners.
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.
Department of Computer Science, Virginia Commonwealth University, Richmond, Virginia, 23284.
Alex
A
Krall
Jonathan
J
Brunn
Spandana
S
Kankanala
Michael H
MH
Peters
D000465:Algorithms; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000037:antagonists & inhibitors; D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D015700:HIV Envelope Protein gp41 / Q000037:antagonists & inhibitors; D057927:Hydrophobic and Hydrophilic Interactions; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D060066:Protein Interaction Maps; D017434:Protein Structure, Tertiary; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors; D012097:Repressor Proteins / Q000037:antagonists & inhibitors
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D015700:HIV Envelope Protein gp41; C106465:MNT protein, human; C489427:MYC protein, human; D010455:Peptides; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors
peptide mimetics; protein-protein interactions; static mapping