Life Sciences Commons^™

Protein Dynamics In Allostery And Computer-Aided Drug Design, Mayar Mohamed

Chemistry Theses and Dissertations

Molecular dynamics (MD) simulation is a powerful and versatile computational tool, that can be used in a wide range of applications from studying complex biological processes such as allostery to investigating the process of the protein-ligand binding in different computer-aided drug design implementations. In this work, various structural and drug discovery projects were performed by combining the state-of-art techniques molecular dynamics simulations, virtual screening, and binding free energy calculations with the innovative Markov State Model analysis and the machine learning techniques.

In the first project, the role of A’a helix as a key player in the transition between the light …

Bayesian Statistical Modeling Of Metagenomics Sequencing Data, Shuang Jiang

Statistical Science Theses and Dissertations

Microbiome count data are high-dimensional and usually suffer from uneven sampling depth, over-dispersion, and zero-inflation. In this thesis, we develop specialized analytical models for analyzing such count data. In Chapter 2, I develop a bi-level Bayesian hierarchical framework for microbiome differential abundance analysis. The bottom level is a multivariate count-generating process that links the observed counts to their latent normalized abundances. The top level is a mixture of Gaussian distributions with a feature selection scheme for differential abundance analysis. A simulation study on both simulated and synthetic data is conducted. A colorectal cancer case study demonstrates that a resulting diagnostic …

Dynamic Mechanisms Of Multidrug Resistance In Human Cancers And Gram Negative Pathogens, Lauren Ammerman

Biological Sciences Theses and Dissertations

This dissertation focuses upon dynamic agents of multidrug resistance (MDR). We used a combination of in silico and in vitro techniques to investigate two membrane transporters that confer MDR – P-glycoprotein, which confers MDR in human cancers, and MtrD, which confers MDR in Neisseria gonorrhoeae. Inhibitors targeting both proteins have tremendous potential for use as co-therapeutics in the treatment of multidrug resistant cancers, or of multidrug resistant infections. However, previously identified inhibitors of P-gp have failed clinical trials due to off-target effects and associated toxicities. Furthermore, the molecular mechanism of antibiotic transport by MtrD is poorly understood, and this dearth …