(376ae) Free Energy Calculation on Human ? Defensin Type 1 in Different Redox Conditions

Human β Defensin type 1 (hBD-1) is a small cationic peptide with three intramolecular disulphide bonds. It is constitutively produced by various epithelial tissues as well as induced in keratinocytes of human skin. It exhibits antimicrobial activity against several microorganisms, but the activity is salt sensitive. Compared to other defensins, it has minor antimicrobial activity in its oxidized form (wildtype) but much stronger activity in reduced form (analogue). In this project, the membrane-translocation capability of hBD-1 in both wildtype and analog forms will be predicted by investigating their free energy barriers crossing three different types of cell membranes: human red blood cell, gram-positive and gram-negative bacteria cells. The human red blood cell membrane is represented by 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine lipid bilayer, while gram-positive and gram-negative bacterial membranes by 1-palmitoyl-2-oleoylglycero-3-phosphoglycerol and 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine lipids in 3:1 and 1:3 molar ratios respectively. Umbrella-sampling method along with coarse-grained technique will be applied to calculate the potential of mean force on hBD-1 crossing different types of lipid membranes. The result will help to uncover the antibacterial dependence of hBD-1 on the redox conditions.