Title: Computer simulations of protein / DNA conformational dynamics
Speaker: Prof. Arjan van der Vaart, Department of Chemistry, University of South Florida
Time: Dec 20th, 2019, Friday 9:30-10:30 AM
Venue: Building 24#-C406
Host: Prof. Yunfei Du
Abstract: Conformational changes are crucial for regulation, signaling and sensing, catalysis, transport and energy conversion in biochemical systems. While the biological function of the conformational dynamics is often understood, the thermodynamic drivers, pathways, triggers and sequence of events are generally unknown. In principle, atomistic molecular dynamics simulations can provide extraordinarily detailed insights into how and why conformational changes happen, but these simulations are challenging due to the limited time scales that can be tackled. We have developed new enhanced sampling methods to overcome these challenges and to quantify thermodynamic aspects of the conformational dynamics. Using these techniques, we have gained insights into the rich conformational dynamics of DNA-binding proteins, which couple DNA bending to binding. Thermodynamic analyses indicate that unlike popular assumptions the binding of these proteins does not involve conformational selection but only induced fit. Applications to unbound DNA showed surprising deviations from elastic models and a marked preference for major groove bending, which is caused by differences in groove hydration. Hydration was also shown to play an important role in determining the natural DNA bending angle in a representative protein-DNA complex. Studies of damaged DNA indicate that modified conformational dynamics play an important role in damage recognition. Our studies highlight the power of enhanced sampling techniques to probe complex systems.