Entropy, Affinity and the Design of Targeted Molecules
Apr 8, Tue 2008
11:00 am, MRB 200 Conference Room
Dr. Michael Gilson
Center for Advanced Research in Biotechnology, University of Maryland,
I will describe new computational methods to model receptor-ligand binding, and intriguing insights they have provided regarding the limits of achievable affinity, the nature and origin of changes in entropy upon binding, and the role of entropy in defining the affinities of small molecules for protein targets. In particular, our calculations of changes in configurational entropy show strong entropy-energy compensation in most cases, but a series of unusual host-guest complexes overcome this compensation to bind with affinities rivaling that of streptavidin and biotin. Applications of these ideas to protein-ligand binding and molecular design will be presented.