############################################################################## Biology 5325 Chemistry & Physics of Biological Molecules Fall 2007 ############################################################################## Class Meetings: Tuesday and Thursday, Lecture, 8:30-10:00, 521 Medical Library Friday, Discussion Section, 1:00-2:00, 521 Medical Library Coursemaster: Jay Ponder (CCB 208, 362-4195, ponder@dasher.wustl.edu) Web Site: http://dasher.wustl.edu/bio5325/ Overall Objective: This course explores the physicochemical basis for the structural integrity, thermodynamic properties and biological functions of proteins, nucleic acids and lipid membranes Suggested Texts: There are no required textbooks. However, the following books may be useful for parts of the course, and are available from online booksellers: Introduction to Protein Structure, 2nd Ed., Branden & Tooze, 1999 Protein Structure and Function, Petsko & Ringe, 2004 Principles of Physical Biochemistry, 2nd Ed., van Holde, Johnson & Ho, 2005 Other Info: Bio 5325 is required by the DBBS Graduate Programs in Biochemistry and in Molecular Biophysics. Lectures coincide with the corresponding Medical School Course, and 1st-year Medical and MSTP students may substitute Bio 5325 for credit. An undergraduate course in Physical Chemistry is recommended prior to enrollment in Bio 5325, but is not formally required. Module 1: Peptides and Proteins: Structure and Folding Aug 30 Protein Taxonomy I: Primary & Secondary Structure Ponder Sep 4 Protein Taxonomy II: Motifs & Supersecondary Structure Ponder Sep 6 Protein Taxonomy III: Tertiary Structure & Fold Types Ponder Sep 7 Protein Folding I: Forces that Determine Structure Ponder Sep 11 Protein Folding II: Mechanisms of Protein Folding Ponder Sep 13 Protein Folding III: Characterization of Folding Pathways Ponder Sep 14 Discussion Section Sep 18 Protein Folding IV: Mutagenesis Studies Ponder Sep 20 Protein Folding V: Structure Prediction & Design Ponder Sep 21 Discussion Section Module 2: Proteins in the Crystal and in Solution Sep 25 X-Ray I: Crystals, Symmetry, Diffraction, Bragg's Law Ellenberger Sep 27 X-Ray II: Structure Factors, Density & Patterson Maps Ellenberger Sep 28 Discussion Section Oct 2 X-Ray III: Phasing by Isomorphous Replacement Ellenberger Oct 4 X-Ray IV: Phasing by Molecular Replacement Ellenberger Oct 5 No Class - Biochemistry/Biophysics Annual Retreat Oct 9 NMR I: Intrinsically Disordered Proteins Hall Oct 11 NMR II: Intrinsically Disordered Proteins Hall Oct 12 Discussion Section Oct 16 NMR III: Protein Dynamics Hall Oct 18 Mid-Term Examination Oct 19 No Class - Fall Break Module 3: Nucleic Acids: Structure and Interactions Oct 23 DNA I: A-, B- and Z-Form Duplex Structures Hall Oct 25 DNA II: DNA Chips, Non-Std Structure, Bending Hall Oct 26 Discussion Section Oct 30 DNA III: Supercoiling, Persistence Length, Electrostatics Hall Nov 1 DNA IV: DNA-Protein Interactions Hall Nov 2 Discussion Section Nov 6 RNA I: Secondary Structure, Thermodynamics & Folding Hall Nov 8 RNA II: Tertiary Structure, UUCG Tetraloops, etc. Hall Nov 9 Discussion Section Nov 13 RNA III: RNA-Protein Interactions Hall Nov 15 X-Ray V: Small-Angle X-Ray Scattering Ellenberger Nov 16 Discussion Section Nov 20 RNA IV: RNA Folding Hall Nov 22 No Class - Thanksgiving Break Nov 23 No Class - Thanksgiving Break Module 4: Membranes and Associated Molecules Nov 27 Membranes I: Historical recognition of membrane Schlesinger properties, barrier and organization functions Nov 29 Membranes II: Lipids, sterols and proteins, Schlesinger biochemical characterization of the lipid bilayer, non-covalent structure Nov 30 Discussion Section Dec 4 Forces Stabilizing Membranes: Hydrophobic and vdW Schlesinger forces, curvature, surface tension/interfacial tension, electrostatic effects Dec 6 Modeling Membranes: Fluidity, diffusion, permeability, Schlesinger lateral and transverse diffusion, chemical & electrostatic potentials Dec 7 Discussion Section Dec 11 Membrane Fusion, Membrane Pore Formation, Detergents Schlesinger and Vesiculation Dec 13 Proteins as Membrane Perturbations: Intrinsic and Schlesinger membrane-associated channels, permeability, transport Dec 18 Final Examination