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Center for Nonlinear Studies |
Tuberculosis, one of the fatal diseases, is caused by Mycobacterium tuberculosis (M. tb.). The most virulence factor of M. tb. is lipoarabinomannan (LAM), which is a glycolipid present in pathogen’s cell envelope. LAM is localized to membrane raft and affects the host immune response by interfering host cell-signaling. M. tb. surface contains mannose-capped LAM (manLAM). Specifically, the mannose-cap portion of LAM is responsible for inhibiting fusion of phagosome with lysosomes- known as P-L fusion, which diminishes the ability of the host macrophages to kill the invading M. tb. Depending on capping, LAM could be more or less pathogenic. LAM could also be used as a biomarker to detect the onset of tuberculosis. Here we study the interaction of mannose-cap (di-mannoside) with the host macrophage membrane mimicked by di-oleoyl-phosphatidy-lcholine (DOPC) lipid bilayer by replica exchange method implemented in GROMACS molecular dynamic package using charmm27 all-atom force field. Through our simulation we are seeking answers to certain questions whether cap is preferred in solution or lipid-water interface and how does cap affect the membrane fluidity and how does these properties change for different membranes.