Chemistry ETDs

Publication Date



Computational simulations use theoretical models to reproduce, as accurately as possible, the observed real-world behavior of complex structures. Guided by experimental observations, many multiscale/coarse-grained simulations seek to explore increasingly complicated systems. Here, a multiscale/coarse-grained simulation program (called TM2) is developed with applications to 1) properties and mechanisms of DNA and DNA polymerases, and 2) adhesion between whole bacterial cells and patterned surfaces. Results from the bacterial adhesion application form a part of a larger collaborative effort aimed at creating multifunctional, controllable surfaces to capture and kill pathogenic bacteria. The application of TM2 is first demonstrated by a coarse-grained model for DNA where the qualitative properties of real B-form DNA arise naturally from local interactions. A preliminary model for small DNA polymerases was also developed which uses the medial axis transform concept to efficiently represent the protein body potential. In another application of TM2, a program named PWA Simulator uses a general free energy functional to simulate the dynamic process of initial cellular attachment to a patterned surface. Another related program (PWA Integrator) integrates a partition function to obtain the equilibrium potential of mean force between a bacterium and a surface. PWA Simulator and PWA Integrator are part of a larger project to build materials with temperature-switchable adhesion properties to capture bacteria, and then to kill them using light-activated biocidal materials. Several deposition and characterization techniques are utilized to fabricate and define complex surfaces with both a temperature-switchable poly(N-isopropylacrylamide) (PNIPAAm) polymer and light-activated biocides (conjugated phenylene ethynylenes, OPEs and PPEs). AFM images of Escherichia coli were able to resolve the physical structure of bacterial surfaces as they were exposed to OPEs and PPEs. The cells show noticeable surface morphology changes, suggesting that the materials directly disrupt outer membrane integrity. Escherichia coli and Staphylococcus aureus were also allowed to adhere to a mixed surface containing PNIPAAm and PPEs. AFM imaging revealed that these surfaces contain randomly mixed areas of both PNIPAAm and biocide. Biocidal testing showed that the addition of PNIPAAm does not decrease the surfaces biocidal potency in the light, suggesting inactivation is caused by light-induced singlet oxygen generation.

Project Sponsors

Defense Threat Reduction Agency-Joint Science and Technology Office for Chemical and Biological Defense (Grant number HDTRA1-11-1-0004)




Biocidal surface, AFM, Atomic Force Microscopy, bacterial adhesion, Biocidal surface, Brownian dynamics, coarse-grained simulations, DNA, DNA model, DNA polymerases, Effective Energy Function, Escherichia coli, computational simulations, multifunctional surface, multiscale simulations, medial axis transform, phenylene ethynylene, poly(N-isopropylacrylamide), PNIPAAm, porin, theoretical model

Document Type


Degree Name


Level of Degree


Department Name

Department of Chemistry and Chemical Biology

First Advisor

Keller, David

First Committee Member (Chair)

Whitten, David G.

Second Committee Member

Cabaniss, Stephen

Third Committee Member

Guo, Hua

Fourth Committee Member

Brozik, James