Quantitative Biosciences Thesis Proposal 

Travis Harrison-Rawn
School of Chemistry and Biochemistry

Advisor: Lynn Kamerlin (School of Chemistry and Biochemistry)

Open to the Community

Loop dynamics of metabolically critical enzymes in mycobacterium tuberculosis
Tuesday, August 25, 2026 at 11:00am

Molecular Science and Engineering (MoSE), Room 1226

Committee Members:

JC Gumbart (School of Physics)
Raquel Lieberman (School of Chemistry and Biochemistry)
Andrew McShan (School of Chemistry and Biochemistry)

Abstract:

Tuberculosis (TB) is the most lethal infectious disease on the planet, taking more than 1.2 million lives per year. While the disease is curable, the pathogenic bacterium mycobacterium tuberculosis, is extremely durable and prone to developing multidrug resistance. The persistence of these variants is an ongoing threat to human health globally and the development of novel therapeutics is urgent.

We propose to computationally characterize enzymes with critical metabolic functions within the bacterium. We will perform physics-based simulations to model the conformational landscapes of triosephosphate isomerase (TPI) and indole-3-glycerol phosphate synthase (IGPS) which take part in glycolysis and tryptophan biosynthesis respectively. 

Structurally, these proteins share a TIM-barrel fold with mobile loops that facilitate ligand coordination required for catalysis. To model these complex conformational changes, we will utilize enhanced sampling simulations in parallel with a dimensionality-reduction technique called time-lagged independent component analysis (tICA). Together, these tools allow us to sample and quantify rare loop transitions at an atomistic resolution. Alongside this approach, we will characterize the allosteric networks that govern these dynamics. Identifying critical allosteric hotspots will enable the screening of selective small molecules aiming to disrupt the loop dynamics essential for catalysis.