Abstract:
Peptides play a crucial role in cellular functions such as protein-nucleic acid interaction
and protein assembly. They are constantly interacting with other cellular components for
various functions. One of the structural classes of peptides is the Poly-L-Proline Helix (PPII).The PPII helices are often present on various protein binding surfaces and act as common binding motifs responsible for various biological activities. This study attempts to predict the binding sites of the PPII peptides. We show that the PPII binding sites are structurally conserved across different protein families, and the PPII can bind there in any orientation regardless of the N or C termini. Using the similarity found across the binding sites within a template dataset of 37 protein structures belonging to 8 different structural families, we have devised a superimpositionbased prediction method for the PPII binding sites. Furthermore, we have validated our method against the template dataset. We were able to predict the binding site for 34 structures correctly. Among these correct binding site predictions, 32 cases show a range of RMSD for native vs. transfer PPII between 0.94˚A to 2.85˚A. In two cases, the RMSD value above 3.5˚A was observed. Since the PPIIs are a conformation class, the study might also help create methodologies for predicting other conformation’s binding sites. The prediction of the binding site of any conformation is beneficial in many aspects, for example - to intervene in protein-nucleic acid interaction around the binding site. Many methods, such as peptidomimetics, are emerging as a tool for drug design and drug delivery. Studying the structures and interactions of various classes of peptides should provide us with the much-required information about the peptide-proteins interactions.
