Computer simulation methods have the power to greatly optimize drug design, reducing the time and cost that it takes to bring a new drug from lab to market. Two factors of concern in rational drug design are the binding affinity of some small molecule to a biomolecular target and the molecule's ability to permeate the cellular membrane to reach said target. In the first half of this work, I describe my efforts analyzing the protein-ligand binding affinity and membrane permeability of inhibitors of the Hv1 proton channel. Hv1 is a voltage-gated proton channel with clinical relevance, being highly expressed in highly metastatic cancer cell lines. The inhibition of Hv1 has been found to slow the growth of cancer cells. My research on Hv1 channel inhibitors lays the groundwork for future studies on adapting these molecules for more effective channel blocking.

In the second half of this work, I examine the tools that are foundational to molecular simulations--force fields--as well as explore the conventional wisdom behind proton assignment in carboxylic acids. Biomolecular simulation represents a valuable computational microscope for drug discovery efforts; however, it is only through correct setup protocols and well-calibrated tools that we can obtain the most accurate and meaningful results.