Bioinformatic Studies on Buffalo Prolactin Derived Anti-Angiogenic Peptide

A 14-amino acid sequence within the buffalo prolactin (buPRL) protein has been identified by BLAST search as similar to that of somatostatin, the gold standard for determining anti-angiogenic activity. A synthetic peptide with the same sequence has been shown to exhibit powerful anti-angiogenic activity, possibly by functioning as a kallikrein-kinin system (KKS) antagonist. In order to further study this peptide’s anti-angiogenic nature, bioinformatics tools were used to analyze its interaction with the bradykinin B1 receptor, which is a component of the KKS. Molecular docking studies were conducted in silico using structures of bradykinin B1 receptor obtained by homology modeling using SWISS-MODEL via the EXPASY web server, as well as a structure of the synthetic peptide that was modeled by the PEP-FOLD de novo modeling server. Docking studies were conducted with the bradykinin B1 structure using the structure of somatostatin and a PEP-FOLD derived structure of a scrambled version of the peptide. All the structures were validated using PDBsum and PROCHECK. Our results indicate that the peptide does form a complex with the bradykinin B1 receptor with a binding energy similar to that of the complex with somatostatin and the scrambled version of the peptide exhibits a similar effect. Further studies, both in silico and wet lab, need to be performed to provide further insights into the mechanism of this 14-amino acid peptide’s anti-angiogenic activity.