The research groups of David Minh, assistant professor of chemistry, and Oscar Juarez, assistant professor of biology, have received an award from the National Institutes of Health (NIH/1R01GM127712-01A1) entitled “Entropy for End-Point and FFT-Based Binding Free Energy Calculations.” The award is for $331,629 in the first year and anticipated to total $1.3 million over four years.
The main objective of this project is to develop better ways to account for entropy in two popular techniques for studying molecular interactions. Specifically, new ways to analyze calculation results will be derived, implemented, assessed, and optimized. The methods will be combined with enhanced sampling techniques.
Minh will also work with Juarez to assess the methods in a drug discovery project. They will use established methods and these new methods to virtually screen a chemical library against a pair of structurally similar bacterial metabolic enzymes; one enzyme is relevant to active and the other to dormant bacteria. Compounds predicted to selectively bind the bacterial (opposed to human) enzymes will be experimentally tested in biochemical assays. The researchers anticipate that their improved methods will be significantly more accurate than established approaches.