I'm hosting Chia-en Chang on Friday June 1. She will give a seminar at 1 pm in BH212; title and abstract below. Chia-en did her graduate work with Mike Gilson and postdoc with Andy McCammon, and has been at UC Riverside for about 4 years now. The mining minima work she will be discussing is some of the most impressive free energy calculations I've seen. http://chem.ucr.edu/chang If you'd like to meet with her, Lili is helping to coordinate her schedule. Title: Insights from Free Energy Calculations: Protein Conformational Equilibrium, Driving Forces and Ligand Binding Processes Abstract: To accurately calculate ligand-protein binding affinity is still challenging in computational chemistry. In this presentation, we used a free energy calculation method, the mining minima algorithm (M2), to compute the binding affinities of various types of inhibitors to p38α MAP kinase. This end-point approach uses an empirical force field and implicit solvent models to find stable conformations in the free and bound states of a system and then compute the binding free energy of each species. Here we selected 30 different p38α inhibitors that can bind to either DFG-in or DFG-out conformations. Notably, some analogs do not have ligand-p38 co-crystal structures. Our computed absolutely binding free energies yield excellent agreement with experimental data and reveal the driving forces of binding. Our results also show the dynamic equilibrium in the DFG-in and DFG-out states and explain why the conformations can co-exist. In addition, I will introduce a novel method to study ligand binding processes in chemical host-guest system. Matthew P. Jacobson Professor, Department of Pharmaceutical Chemistry Department of Bioengineering and Therapeutic Sciences California Institute for Quantitative Biosciences Director, Graduate Group in Biophysics UCSF MC 2540 1700 4th St., Byers Hall, Room 408E San Francisco, CA 94158-2330 matt.jacobson@ucsf.edu<mailto:matt.jacobson@ucsf.edu> jacobsonlab.org<http://jacobsonlab.org>