A Multi-Scale Molecular Dynamic Approach to the Study of the Outer Membrane of the Bacteria Psudomonas Aeruginosa PA01 and the Biocide Chlorhexidine
Van Oosten, Brad
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The introductory chapters of this thesis contains an explanation to the methods and basic theory of the molecular dynamics approach. Together with the appendix section, in which a step by step tutorial how to set up and run basic simulations using the gromacs software is presented, this thesis can serve as an introductory aid in performing molecular dynamics simulations. In the research portion of this thesis, I provide several uses for the molecular dynamics approach applied to the biocide chlorhexidine as well as the study of membranes, including a mimic of the bacteria membrane of Pseudomonas Aeruginosa PA01. The motivation for this research was previous work done in our lab which determined that chlorhexidine has a high affinity for DMPC and found the depth at which it resides in a model DMPC membrane. From this information, an all-atom representation of chlorhexidine was made, which was proven to reproduce the experimental results. While we learned much about chlorhexidine in a model DMPC membrane, this study lacked the destruction of the membrane as well as the study of chlorhexidine in a biologically relevant membrane. For these reasons coarse grained versions of the all-atom chlorhexidine models as well as a new lipopolysaccharide molecule was created. With the coarse grained model of chlorhexidine and the ability to create a bacterial membrane mimic, the study of chlorhexidine and other antibacterial agents can be further studied.