Identifikasi Determinan Molekul Interaksi STK630921 pada Interleukin-17A

Abstract

Interleukin-17A (IL-17A) is a pro-inflammatory cytokine that is involved in the pathogenesis of several diseases, including psoriasis, rheumatoid arthritis, cancer, diabetes, and end-stage kidney disease. Increased serum levels of IL-17A provide a clue of the association between IL-17A in the incidence of diabetic nephropathy. This association was also clarified by the finding that inhibition of IL-17A activity can reduce albuminuria, kidney injury and can delay the progression of diabetic nephropathy. This role of IL-17A makes it a potential target of choice for the treatment of diabetic nephropathy, which so far relies on optimal control of the renin-angiotensin system. This study aims to identify the molecular determinants of the STK630921 interaction to IL17A. The experiment was conducted by docking the STK630921 molecule to the protein IL-17A, followed by molecular dynamics simulation for 15 ns. Identification of molecular determinants was carried out using the PyPLIF-HIPPOS software on the molecular dynamics simulation results. This study succeeded in identifying amino acids that play an important role, namely His29, Trp67, Asn27, Lys114 and Glu95 with aromatic interactions and hydrogen interactions as the types of interactions that play an important role in the activity of STK630921 in the protein structure of 4HR9.