IN SILICO IDENTIFICATION OF NOVEL LIGAND ENHANCES MYELOPOIESIS TO PREVENT INFECTION CAUSED AFTER CHEMOTHERAPY

Abstract

Myelopoiesis is required in order to prevent infection during bone marrow transplantation and to build enhanced immune systems in patients. In this study our aim is to enhance HSC myelogenesis and minimise erythropoiesis, this can be done with the help of regulation of various transcription factor. PU.1 is a member of the ETS family of Transcription Factors and it plays an important role in the adaptive immune system. Transcription factor c-Jun binds with PU.1 β3/β4 and leads to Myelopoiesis. However, GATA-1 competes for the binding site with c-Jun to bind with PU.1, its binding leading to Erythropoiesis. However, the molecular mechanism underlying this interaction is not known and a lot of inconsistencies exist in literature. Therefore, the PU.1 binding motifs of GATA-1 and c-Jun should be docked with PU.1. This can reveal the mechanism of PU.1 binding with GATA-1 and c-Jun which will help in identification of most hotspot residues which take part in interaction. It has been reported in papers that the GATA-1 mediated repression of PU.1 can be abolished if the physical interaction between the two proteins is modified. Therefore, we need to design a PU.1 β3/β4 region Mimetic Peptide Library to find a suitable antagonist that would specifically bind to GATA-1, inhibiting it to bind to PU.1 and allowing c-Jun to bind with PU.1, and lead to Myelopoiesis.