Text: None assigned; reference books on Reserve in the Woodward or Main Libraries
References: First half of course: Cantor & Schimmel, Biophysical Chemistry, Part III; Chapter 15. (Woodward)
Second half of course: Flory, Principles of Polymer Chemistry, Chapters XII and XIII (Mail Library) Hiemenz, Polymer Chemistry, Chapter 8 (Main Library)
Course Outline:
The chemistry of biological processes typically involves macromolecules (e.g., proteins, nucleic acids) interacting with small or large molecules in solution both as catalysts in enzymatic reactions and as partners in binding or exclusion reactions. In this course we will focus on those interactions which do not involve covalent bond formation or rupture. Binding events are involved in virtually all biochemical reactions while macromolecular exclusion may have been responsible for the origin of biological cells. We therefore will begin by treating simple, monovalent ligand binding in independent and cooperative interactions. Divalent, neutral ligand binding to regular lattices will follow, then the effects of charge-charge interactions on binding will be examined and methods of analysis particularly suited to binding of charged species considered. Because in the cell cytoplasm protein concentrations can exceed 30% by weight, we next will look at treatments of concentrated macromolecular solutions and discuss the origin of such excluded volume effects as phase separation in macromolecular mixtures. The treatment originates from studies of polymer solutions and has been invoked in origin of life theories. If time permits, protein exclusion effects (macromolecular crowding) will be explicitly discussed.
Approximate Topic Schedule
Week 1 & 2: Neutral ligand binding to macromolecules; statistics of multi-site binding; micro & macro equilibrium constants; independent binding; cooperativity
Week 3 - 5: Divalent ligand binding to a lattice; binding of charged ligands to charged sites; monovalent and divalent ion binding; measurement of association constants by electrophoresis; zeta potentials
Week 6 - 11 Flory-Huggins mean field theory of polymer solutions: free energy of mixing of polymer on a lattice; chemical potentials; theta conditions; phase separation of a binary polymer solution; upper and lower critical solution temperatures; thermodynamic behaviour of n-component polymer solutions; macromolecular partition in phase separated polymer solutions
Week 12 - 13 Complex coacervation; theories of origin of biological cells; excluded volume effects in concentrated protein solutions