Investigating the differences in interaction of isomeric isoamphipathic oligothioetheramides with lipid bilayer membranes using molecular dynamics simulations
Antibacterial oligothioetheramides have been fabricated by Prof. Christopher Alabi's group at Cornell University as a possible alternative to current antibiotics, to combat the continuous rise in antibiotic resistance that bacteria have been developing. These oligothioetheramides have similar antibacterial properties as antimicrobial peptides. While the exact mechanism is not known in both cases, it is accepted that due to their inherent positive charge these molecules are attracted to negatively charged bacterial membranes. They insert into the membranes and disrupt the structural integrity of the membrane leading to cell death. Oligothioetheramides, however, do not have the same drawbacks as the peptides as they are resistant to proteolytic degradation and the production procedure developed by Prof. Alabi's lab allows great control over their backbone during assembly. Experiments have shown that these oligthioetheramides have many of the same factors affecting their activity, which are their charge, hydrophobicity and the ratio between the two. This is by no means an exhaustive list. Further experiments by the Alabi lab showed that two oligomers that are meta- and para- isomers of each other had a tenfold difference in their anti-bacterial potency. The para-isomer was more effective than the meta-isomer, even though they have the same charge and hydrophobicity. We have performed atomistic molecular dynamics simulations to investigate the thermodynamic differences in the process between the two isomers as they approach bacterial and mammalian cell membrane mimics and calculated the binding energy of the isomers with the membranes.
Antibiotics; Biomolecules; Computation; Materials
Alabi, Christopher Akinleye
M.S., Chemical Engineering
Master of Science
dissertation or thesis