8231 (Medical School Campus)
protein biophysics, molecular simulation, Markov state models, allostery, drug design
We combine computer simulations and experiments to understand the distribution of different structures a protein adopts and how this ensemble determines a protein’s function. Our overarching objectives are (1) to understand how drugs and mutations exert allosteric control over distant sites and (2) to design drugs and mutations that exploit proteins’ conformational heterogeneity to control function. Examples of ongoing projects include (1) understanding how mutations give rise to antibiotic resistance, (2) designing allosteric drugs to combat antibiotic resistant infections, (3) understanding allosteric networks in G proteins and designing allosteric anti-cancer drugs, and (4) understanding and interfering with the mechanisms of Ebola infection. To facilitate these applications, we also develop enhanced sampling algorithms for simulating long timescale dynamics of proteins and nucleic acids.