Biochem 440B, Physical Biochemistry-I

Fall 2009

Principles of Thermodynamics and Kinetics and their Applications to Biological Macromolecules

Classes on Tuesdays and Thursdays from 10:00 to 11:50 in 217 Noyes Lab

Help Sessions are scheduled each Wednesday at 7pm in room 217 Noyes Lab

PART 1:  5 LECTURES (Gennis) - Aug 25, 27; Sept 1, 3, 8 (Lectures 1-5)

A     The Principles of Thermodynamics                        

            1. First Law - System & surroundings; work & heat; mechanical energy and force;

            2. Energy exchanges; enthalpy; bond energies

            3. Entropy - probabilities & microscopic distributions

            4. Approach to equilibrium - free energy and chemical work, ∆G, ∆G°, K

            5. Temperature & pressure dependence of equilibrium; non-bonding interactions

            6. Chemical potentials; standard states - acid-base, pH, redox potentials

            7. Coupling between reactions, and biological energy conversion

PART 2:  9 LECTURES (Nair):  Sept 10, 15, 17, 22, 24, 29; Oct 1, 6, 8 (Lectures 6-14)

A.    Water, Membranes and the Hydrophobic Force -                                                             

                                    (Gennis text)

            1.    Structure of liquid water.

2.    Hydrophobic effect

3.     Amphiphiles, micelles and the phospholipid bilayer

B.    Structural Hierarchy of Proteins and the Forces Involved

                                    (Gennis text;Nair notes)

            1. Proteins: Review Ramachandran + secondary structure; protein folds + motifs

            2. Non-bonding forces - steric interactions, electrostatics;

            3. Coulomb's Law and applications - ion-ion, ion-dipole, various dipoles

            4. Dielectric properties, polarizability; van der Waals dispersion forces

            5. Hydrophobicity and amphiphilicity of protein helices

C. Protein Stability -                                                    

                                    (Nair notes, Gennis text)

            1. Two state equilibrium treatment of protein folding;  ∆H,  ∆S,  ∆Cp, etc

            2. Hydration and solvent effects: osmotic pressure, denaturants, stabilizers, etc

            3. Hydrophobicity, packing, mutagenesis - ∆∆G

D.    Nucleic Acid Structure/Topology/Stabilitiy -

                                    (Nair notes, Gennis text)

            1. Nucleic Acids: Phosphate torsions, ring conformers, base-pairing

            2. Chain conformers, base pairing - Watson-Crick, Hoogstein; DNA polymorphism

            3. DNA melting & renaturation; nearest neighbor analysis

            4. DNA topology and supercoiling- twists, writhe, nicks & knots                      

            5. RNA structures - stems, loops, tetraloops, etc

FIRST EXAMINATION: Tuesday, October 13

PART 3: 8 LECTURES (Gennis) Oct 15, 20, 22, 27, 29, Nov. 3, 5, 10 (Lectures 15-22)

A.     Ligand binding and recognition

            1.  Affinity and kinetics; binding isotherms

            2.  Binding models - single vs. multiple sites, independent vs. cooperative binding

            3.  Binding & linkage - energetics of coupling

            4. Allosteric regulation of proteins

B. 5. Isothermal titration calorimetry

C. Biochemistry of transport, bioenergetics

6. Biochemistry of transport

7. Coupling through linked transport processes

Part 4: 5 LECTURES (Nair) Nov. 12, 17

(Nov. 19 second exam)

(Nov 24-28, Thanksgiving)

Dec 1, 3, 8 (Lectures 23-27)

 A.    Principles of Chemical Kinetics -   

1.      Kinetic theory, diffusion and collision rates: Fick’s laws

2.      Reaction kinetics; order of reaction; diffusion control

3.      Activation energy; the transition state and Marcus theory; the reaction coordinate

4.      Rate constants and the equilibrium constant

B.    Enzyme Kinetics and Catalysis -              

            1. Transition state complexes; binding, strain and catalysis

            2. Steady state: M-M kinetics; competitive/non-competitive inhibition, etc

            3. More complex kinetics - order of addition, etc.

            4. Pre-steady state approach to enzyme kinetics; perturbation/relaxation methods

C.    Protein Folding Kinetics -

FINAL EXAMINATION, 1:30 – 4:30 PM, Wednesday, December 16

GRADING:

2 EXAMINATIONS IN CLASS: 25% EACH

1 FINAL EXAM:  25%

10-12 PROBLEM SETS: 2 POINTS (MAX) EACH, ONLY IF TURNED IN ON TIME: 25%