Computer Simulation of Antimicrobial Agents

Abstract

The last 18 months has shown the impact a single microorganism can have on society with the SARS-CoV-2 virus. This is not the only global threat on our health, with the World Health Organisation and other government agencies warning against the increase in antimicrobial resistance today. Antimicrobial peptides have been seen as a possible solution, as they are known to fight bacteria as a part of the immune system and there is a high variety of molecules.

This thesis uses molecular dynamic simulation to look into two different cyclic peptides, mrs-002 and tkbs-013, as possible antimicrobial peptides to determine their interactions and effects on a POPE:POPG lipid bilayer membrane. Different systems were set up for this thesis for conformational analysis of the peptides and to investigate the peptide-membrane interactions and their effect on the membrane themselves.

It was found that the mrs-002 and tkbs-013 was most likely biologically active from their interactions and the effects than had, with mrs-002 having stronger interactions and effects overall. Visual analysis of the interactions and positions of the peptides suggested the mrs-002 peptide either using the barrel-stave or the toroidal method as mode of attack, while the tkbs-013 peptide seemed to suggest a combination of the carpet and the barrel-stave or toroidal method against the lipid bilayer. Their conformational analysis showed that the mrs-002 had some sterical hindrance compared to tkbs-013, but that none of the peptides seem to favour any secondary structure.