Streptavidin-biotin binding energetics

The high affinity energetics in the streptavidin-biotin system provide an e xcellent model system for studying how proteins balance enthalpic and entro pic components to generate an impressive overall free energy for ligand bin ding. We review here concerted site-directed mutagenesis, biophysical, and computational studies of aromatic and hydrogen bonding interaction energeti cs between streptavidin and biotin. These results also have provided insigh t into how streptavidin builds a large activation barrier to dissociation b y managing the enthalpic and entropic activation components. Finally, we re view recent studies of the biotin dissociation pathway that address the fun damental question of how ligands exit protein binding pockets. (C) 1999 Pub lished by Elsevier Science B.V. All rights reserved.