Speaker
Description
Toll-like receptors (TLRs) primarily involved in recognizing pathogen-associated molecular patterns (PAMPs) and innate immune activation against invading pathogens. Simultaneous cytokine storm generated through uncontrolled activation of TLRs remains a challenge in management of certain disease conditions, such as sepsis. Very few studies have reported peptide binding partners for TLR-2 as modeling studies on peptide are time consuming and difficult to run using local hosts. In this study, using high-performance computing facility, we reported the designing and modeling studies of short peptide inhibitors of TLR-2. Initially, reported anti-inflammatory peptide were collected from various databases and filtered with predefined criteria. Total 29 short peptides passing the initial screen were docked with TLR-2 structure in BioLuminate program (Schrodinger LLC). Top docking poses of peptides were studies through molecular dynamic simulations. The peptide forming stable complex were then considered for mutational studies. Around 180 mutants of five top ranked peptides were designed and followed by docking studies. Further, top docking poses were analyzed by molecular dynamic simulations. The peptide forming least energy complex with TLR-2 were synthesized and evaluated using in vitro studies. These initial evaluations show promising application of this peptide in therapeutics as well as developing novel drug delivery systems.
