Chemistry & Physics of Biological Molecules

Biology 5325 / Medical School M15

Fall Term 2007

Coursemaster: Jay Ponder

General Information

Syllabus & Schedule [TEXT] [PDF]

Lecture Summaries

Lecture 1 (Aug 30): Protein Taxonomy I: Primary & Secondary Structure [PDF]

Lecture 2 (Sep 4): Protein Taxonomy II: Motifs & Supersecondary Structure [PDF]

Lecture 3 (Sep 6): Protein Taxonomy III: Tertiary Structure & Fold Types [PDF]

Lecture 4 (Sep 7): Protein Folding I: Forces that Determine Structure [PDF]

Lecture 5 (Sep 11): Protein Folding II: Mechanisms of Protein Folding [PDF]

Lecture 6 (Sep 13): Protein Folding III: Characterization of Folding Pathways [PDF]

Lecture 7 (Sep 18): Protein Folding IV: Mutagenesis Studies [PDF]

Lecture 8 (Sep 20): Protein Folding V: Structure Prediction & Design [PDF]

Lecture 9 (Sep 25): X-Ray I: Introduction to Crystallography [PDF]

Lecture 10 (Sep 27): X-Ray II: Crystals & Crystallization [PDF] Data Collection [PDF]

Lecture 11 (Oct 2): X-Ray III: Phasing by Isomorphous Replacement [PDF]

Lecture 12 (Oct 4): X-Ray IV: Phasing by Molecular Replacement [PDF]

Lecture 13 (Oct 9): NMR I: Intrinsically Disordered Proteins [PDF]

Lecture 14 (Oct 11): NMR II: More on Intrinsically Disordered Proteins [PDF]

Lecture 15 (Oct 16): NMR III: Protein Dynamics [PDF]

Lecture 16 (Oct 23): DNA I: A-, B- and Z-Form Duplex Structures

Lecture 17 (Oct 25): DNA II: DNA Chips, Non-Std Structure, Bending [PDF]

Lecture 18 (Oct 30): DNA III: Supercoiling, Persistence Length, Electrostatics [PDF]

Lecture 19 (Nov 1): DNA IV: DNA-Protein Interactions [PDF]

Lecture 20 (Nov 6): RNA I: Secondary Structure, Thermodynamics & Folding [PDF]

Lecture 21 (Nov 8): RNA II: Tertiary Structure, UUCG Tetraloops, etc. [PDF]

Lecture 22 (Nov 13): RNA III: RNA-Protein Interactions [PDF]

Lecture 23 (Nov 15): X-Ray V: Small-Angle X-Ray Scattering [PDF]

Lecture 24 (Nov 20): RNA IV: RNA Folding [PDF]

Lecture 25 (Nov 27): Membranes I: History, Organization & Functions [PDF]

Lecture 26 (Nov 29): Membranes II: continued from Nov 27....

Lecture 27 (Dec 4): Membranes III: Stabilizing Forces, Fluidity, etc. [PDF]

Lecture 28 (Dec 6): Membranes IV: continued from Dec 4....

Lecture 29 (Dec 11): Membranes V: Interactions with Proteins [PDF]

Lecture 30 (Dec 13): Membranes VI: Mechanism of Fusion [PDF]

Problem Sets and Exams

Problem Set 1 [PDF] Answers [PDF]

Problem Set 2 [PDF] Answers [PDF]

Problem Set 3 [PDF] Answers [PDF]

Problem Set 4 [PDF]

Problem Set 5 [PDF] Answers [PDF]

Problem Set 6 [PDF]

Examination 1 [PDF] Answers [PDF]

Problem Set 7 [PDF]

Examination 2 [PDF]

Handouts & Reading

Protein Structure & Taxonomy

The Anatomy and Taxonomy of Protein Structure, J. S. Richardson,
[Updated by D. C. Richardson and J. S. Richardson, 2000-2007]
Advances in Protein Chemistry, 34, 167-339 (1981) [PDF]

Looking at Proteins: Representations, Folding, Packing, and Design,
J. S. Richardson, D. C. Richardson, N. B. Tweedy, K. M. Gernert, T. P. Quinn,
M. H. Hecht, B. W. Erickson, Y. Yan, R. D. McClain, M. E. Donlan and M. C. Surles,
Biophysical Journal, 63, 1186-1209 (1992) [PDF]

Rules for Alpha Helix Termination by Glycine, R. Aurora, R. Srinivasan
and G. D. Rose, Science, 264, 1126-1130 (1994) [PDF]

Protein Stability & Folding

Measuring the Conformational Stability of a Protein,
C. N. Pace and J. M. Scholtz,
from Protein Structure: A Practical Approach, 2nd Edition,,
edited by T. Creighton, pg 299-321, Oxford University Press, 1997 [PDF]

Mutant Sequences as Probes of Protein Folding Mechanisms,
C. R. Matthews and M. R. Hurle, Bioessays, 6, 254-257 (1987) [PDF]

Protein Stability Curves, W. J. Becktel and J. A. Schellman,
Biopolymers, 26, 1859-1877 (1987) [PDF]

Understanding Protein Folding via Free-Energy Surfaces
from Theory and Experiment,
A. R. Dinner, A. Sali, L. J. Smith, C. M. Dobson and M. Karplus,
Trends in Biochemical Sciences, 25, 331-339 (2000) [PDF]

The Protein Folding "Speed Limit", J. Kubelka, J. Hofrichter and W. A. Eaton,
Current Opinion in Structural Biology, 14, 76-88 (2004) [PDF]

Protein Engineering & Design

De Novo Protein Design: Fully Automated Sequence Selection,
B. I. Dahiyat and S. L. Mayo, Science, 278, 82-87 (1997) [PDF]

Design of a Novel Globular Protein Fold with Atomic-Level Accuracy,
B. Kuhlman, G. Dantas, G. C. Ireton, G. Varani, B. L. Stoddard and D. Baker,
Science, 302, 1364-1368 (2003) [PDF]

Computational Design of a Single Amino Acid Sequence that Can Switch
between Two Distinct Protein Folds, X. I. Ambroggio and B. Kuhlman,
Journal of the American Chemical Society, 128, 1154-1161 (2006) [PDF]

Computational Design of Receptor and Sensor Proteins with Novel Functions,
L. L. Looger, M. A. Dwyer, J. J. Smith and H. W. Hellinga,
Nature, 423, 185-190 (2003) [PDF]

Crystallography & Microscopy

X-Ray Diffraction, from Principles of Physical Biochemistry,
K. E. van Holde, W. C. Johnson and P. S. Ho,
chapter 6, pg 242-311, Prentice-Hall, Inc., 1998 [PDF]

X-Ray Diffraction and the Determination of Molecular Structure,
from Physical Chemistry with Applications to the Life Sciences,
D. Eisenberg and D. Crothers, pg 798-846, Benjamin/Cummings, Inc., 1979 [PDF]

1.8 Ang Bright State Structure of the Reversibly Switchable Fluorescent
Protein Dronpa Guides the Generation of Fast Switching Variants,
A. C. Stiel, S. Trowitzsch, T. Weber, M. Andersen, C. Eggeling, S. W. Hell,
S. Jakobs and M. C. Wahl, Biochemical Journal, 402, 35-42 (2007) [PDF]

Resolution of Lambda/10 in Fluorescence Microscopy Using Fast Single
Molecule Photo-Switching, C. Geisler, A. Schonle, C. von Middendorff,
H. Bock, C. Eggeling, A. Egner and S. W. Hell,
Applied Physics A, 88, 223-226 (2007) [PDF]

Intrinsically Disordered Proteins

Intrinsically Unstructured Proteins and Their Functions,
H. J. Dyson and P. E. Wright,
Nature Reviews Molecular Cell Biology, 6, 197-208 (2005) [PDF]

Characterization of Segments from the Central Region of BRCA1:
An Intrinsically Disordered Scaffold for Multiple Protein-Protein and
Protein-DNA Interactions?, W.-Y. Mark, J. C. C. Liao, Y. Lu, A. Ayed,
R. Laister, B. Szymczyna, A. Chakrabartty and C. H. Arrowsmith,
Journal of Molecular Biology, 345, 275-287 (2005) [PDF]

NMR Spectroscopy

Spin Dynamics: Basics of Nuclear Magnetic Resonance,
M. H. Levitt, chapters 1-3, pg 5-68, John Wiley and Sons, 2001 [PDF]

Nucleic Acids

Microarray Detection of Duplex and Triplex DNA Binders
with DNA-Modified Gold Nanoparticles,
A. K. R. Lytton-Jean, M. S. Han and C. A. Mirkin,
Analytical Chemistry, 79, 6037-6041 (2007) [PDF]

A General Purpose RNA-Cleaving DNA Enzyme,
S. W. Santoro and G. F. Joyce,
Proceedings of the National Academy of Sciences USA,
79, 4262-4266 (1997) [PDF]

The Catalytic Diversity of RNAs, M. J. Fedor and J. R. Williamson,
Nature Reviews Molecular Cell Biology, 6, 399-412 (2005) [PDF]

The Speed of RNA Transcription and Metabolite Binding
Kinetics Operate an FMN Riboswitch,
J. K. Wickiser, W. C. Winkler, R. R. Breaker and D. M. Crothers,
Molecular Cell, 16, 49-60 (2005) [PDF]

NMR Structure of the Bacteriophage Lambda N Peptide/boxB RNA Complex:
Recognition of a GNRA Fold by an Arginine-Rich Motif,
P. Legault, J. Li, J. Mogridge, L. E. Kay and J. Greenblatt,
Cell, 93, 289-299 (1998) [PDF]

Kinetic Redistribution of Native and Misfolded RNAs
by a DEAD-Box Chaperone, H. Bhaskaran and R. Russell,
Nature, 449, 1014-1018 (2007) [PDF]

X-Ray Scattering

Conformational Changes of p97 during Nucleotide Hydrolysis
Determined by Small-Angle X-Ray Scattering,
J. M. Davies, H. Tsuruta, A. P. May and W. I. Weis,
Structure, 10, 183-195 (2005) [PDF]

Membrane Fusion

Ensemble Molecular Dynamics Yields Submillisecond
Kinetics and Intermediates of Membrane Fusion,
P. M. Kasson, N. W. Kelley, N. Singhal,
M. Vrljic, A. T. Brunger and V. S. Pande
Proceedings of the National Academy of Sciences USA,
103, 11916-11921 (2006) [PDF]

Control of Membrane Fusion Mechanism by Lipid Composition: Predictions
from Ensemble Molecular Dynamics, P. M. Kasson and V. S. Pande,
PLOS Computational Biology, 3, 2228-2238 (2007) [PDF]

Molecular Modeling Software

Software Information [TEXT]

KineMage [DIR]

RasMol [DIR]

PyMOL [DIR]