Event Information
Thermodynamic Basis of Additivity in Ligand Binding: Matrix Metalloproteinase-3
- Abstract:
Despite recent advances in synthetic organic chemistry, computational chemistry and structural biology, the molecular basis of affinity in aqueous solution remains poorly understood. Additivity is a frequently invoked concept in ligand binding. In the late 1970’s, Jencks noted that the energetic consequence of linking two conceptual fragments, A and B, into a single AB ligand had an indeterminate effect on the energetics of ligand binding. Using matrix metalloproteinase-3 (stromelysin-1) as a model system, two series of linkage ligands were created to investigate the origin and nature of the Jencksian interaction energy. Contrary to previous speculation that such energies are primarily entropic in origin, our data demonstrate that, at least for stromelysin-1, additivity is an enthalpic phenomenon. Possible molecular origins of this behavior and their consequences for ligand design will be discussed.
Ph.D. Dissertation Defense Examination Seminar
Student Exams Seminar