Abstract
Antibiotic resistance is on the rise and only two new classes of antibiotics have been approved by the FDA in the past 25 years, so alternatives to antibiotics may be worth considering. Antimicrobial peptides exist in virtually all prokaryotes, archaea, and eukaryotes and have an important function in the immune system. Antimicrobial peptides have broad-spectrum activity against microbes by four mechanisms: forming ion channels or pores across the cell membrane, inhibiting cell wall biosynthesis, RNase or DNase activity, and binding to receptors to depolarize and perforate the cell membrane. Of the ion channel or pore mechanism, the three most cited models of antimicrobial activity are the barrel-stave, toroidal pore, and carpet models. Maximin 3 is an alpha helix 27 amino acids long and is part of Bombina maxima’s epithelial defenses, but its model of action is unknown. This research used GROningen MAchine for Chemical Simulations (GROMACS) version 5.0.1 to simulate the interaction of Maximin 3 with a cell membrane to find out which model might apply. First, some of the KALP_15 in a membrane of dipalmitoylphosphatidylcholine (DPPC) tutorial was followed using GROMACS, substituting Maximin 3 for KALP_15. The topology was then generated, Maximin 3 was inserted through a properly-sized membrane of DPPC, and both were solvated with H_2O. The rest of the tutorial will be adding dissolved ions, energy minimization, equilibration, molecular dynamics, and final analysis. Membranes of DPPC are mammalian-type, so data from the KALP_15 in a membrane of DPPC tutorial might then be used to identify and attempt to minimize the toxic effects of Maximin 3 on mammals. Then the membrane needs to be switched from a neutrally charged mammalian-type membrane of DPPC to a negatively charged bacterial-type membrane of dipalmitoylphosphatidylglycerol (DPPG) so GROMACS can be run again to find the model of Maximin 3 antimicrobial activity.
