Coursemaster:
Tim Lohman
Department of Biochemistry
and Molecular Biophysics
2801 North Bldg.
362-4393
email:
lohman@biochem.wustl.edu
Pre-requisites: General Biochemistry, Physical Chemistry (thermodynamics and kinetics), Calculus, Differential equations
All biological processes require the interaction of a number of macromolecules with each other as well as with small ligand effectors in order to carry out a particular function in a precise, controlled manner. In some cases, these interactions are long-lived; however, in most cases, transient interactions are essential for proper control of biological function. Even "isolated" ligand-macromolecule interactions and/or conformational transitions are linked to other binding and/or conformational transitions, hence all macromolecular interactions are composed of multiple equilibria. The focus of this course is to introduce you to the quantitative approaches and logic needed to define these multiple equilibrium processes and to begin to dissect them in order to understand the forces involved in stabilizing and regulating the function of these macromolecules. This requires investigations of the energetics, thermodynamics (stabilities, affinities), kinetics and mechanism of binding and enzyme catalysis, including both steady state and transient (pre-steady state) approaches.
This course will discuss the theoretical principles, logic and approaches used to study these processes from a quantitative perspective. Topics will include thermodynamics, multiple binding equilibria, analysis of binding isotherms, Wyman linkage relationships, cooperativity, allostery, macromolecular assembly, enzyme catalysis and mechanism, steady-state and pre-steady state kinetics. Some techniques used to study binding processes will also be discussed. A major goal is for the student to use computer simulation and non-linear least squares methods to aid in the analysis of both equilibrium binding isotherms and kinetic time courses.
The following books will be used as the main references for the course, although these will be supplemented with current research articles.
- Binding and Linkage-Jeffries Wyman and Stanley J. Gill (University Science Books)
- Kinetics for the Life Sciences-H. Gutfreund (Cambridge University Press)