Artificial intelligence channelizing protein-peptide interactions pipeline for host-parasite paradigm in IL-10 and IL-12 reciprocity by SHP-1

Abstract

Identification of molecular targets in any cellular phenomena is a challenge and a path that one endeavors upon independently. We have identified a phosphatase SHP-1 as a point of intervention of IL-10 and IL-12 reciprocity in leishmaniasis. The therapeutic model that we have developed uniquely targets this protein but the pipeline in general can be used by the researchers for their unique targets. Naturally occurring peptides are well known for their biochemical participation in cellular functions hence we were motivated to use this uniqueness of physico-chemical properties of peptides conferred by amino acids through machine learning to channelize a mode of therapeutic exploration in infectious disease. Using computational approaches, we identified high order sequence conservation and similarity in SHP-1 sequence which was also evolutionarily conserved, complete structure of Mouse SHP-1 was predicted and validated, a unique motif of the same was identified against which library of synthetic peptides were designed and validated followed by screening the library by docking them with MuSHP-1 protein structure. Our findings showed 3 peptides had high binding affinity and in future can be validated using cell based and in vivo assays.