Chemistry & Physics of Biomolecules

Biology 5357

Fall Term 2021

Coursemaster: Jay Ponder


General Information

Syllabus & Schedule [PDF]


Lecture Summaries

Lecture 01 (Aug 30): Protein Taxonomy I: Primary & Secondary Structure [PDF] [Video-2020]

Lecture 02 (Sep 01): Protein Taxonomy II: Motifs & Supersecondary Structure [PDF] [Video-2020]

Lecture 03 (Sep 03): Protein Taxonomy III: Tertiary Structure & Fold Types [PDF] [Video-2020]

Lecture 04 (Sep 08): Protein Folding I: Forces that Determine Structure [PDF] [Video]

Lecture 05 (Sep 10): Protein Folding II: Mechanisms of Protein Folding [PDF] [Video]

Lecture 06 (Sep 13): Protein Folding III: Mutagenesis Studies of Folding & Stability [PDF] [Video]

Lecture 07 (Sep 15): Intrinsically Disordered Proteins & Their Biological Significance [PDF] [Video]

Lecture 08 (Sep 17): Experimental Techniques for Studying IDRs [PDF] [Video]

Lecture 09 (Sep 20): Basics of Molecular Dynamics & Monte Carlo Simulation [PDF] [Video]

Lecture 10 (Sep 22): Sampling Methods & Free Energy Calculations [PDF] [Video]

Lecture 11 (Sep 24): Mutagenesis Experiments & Protein Design [PDF] [Video]

Lecture 12 (Sep 27): Protein Structure Prediction & DeepMind's AlphaFold [PDF] [Video]

Lecture 13 (Sep 29): Theoretical Methods & Case Studies for IDRs [PDF] [Video]

Lecture 14 (Oct 04): Polymer Statistics I: Basic Theory [PDF] [Video]

Lecture 15 (Oct 06): Polymer Statistics II: Real Chains & Applications [PDF] [Video-2020]

Lecture 16 (Oct 08): Polymer Statistics III: Mixtures of Polymers [PDF] [Video]

Lecture 17 (Oct 13): Nucleic Acid Components & Their Assembly [PDF] [Video-2020]

Lecture 18 (Oct 15): Structure, Conformation & Bending of A, B & Z DNA [PDF] [Video]

Lecture 19 (Oct 18): Triple Stranded, Quadruplex and Other Structures [PDF] [Video-2020]

Lecture 20 (Oct 22): Introduction to RNA Biology [Video]

Lecture 21 (Oct 25): MALAT1 as a Model System [PDF]

Lecture 22 (Oct 27): Nucleic Acid-Protein Binding Interactions [PDF] [Video]

Lecture 23 (Oct 28): RNA Acting as Enzymes: Ribozymes & Riboswitches [PDF] [Video-2020]

Lecture 24 (Nov 01): Basic Principles of Electron Microscopy [PDF] [Video]

Lecture 25 (Nov 03): Electron Microscopy & Biomolecular Assemblies [PDF] [MP4]

Lecture 26 (Nov 08): Introduction to Glycobiology [PDF] [Video]

Lecture 27 (Nov 10): Glycan Structure & Analysis Methods [PDF] [Video]

Lecture 28 (Nov 12): Classes of Glycoproteins & Glycolipids [PDF] [Video]

Lecture 29 (Nov 15): Carbohydrate-Related Biology & Disease States [PDF] [Video]

Lecture 30 (Nov 17): Glycan Recognition in Cell Adhesion & Signaling [PDF] [Video]

Lecture 31 (Nov 19): Discovery of the Membrane & Embedded Proteins [PDF] [Notes] [Video]

Lecture 32 (Nov 22): Chemical Composition of the Cell Membrane [PDF] [Notes] [Video]

Lecture 33 (Nov 29): Membrane Structure & Mechanics [PDF] [Notes] [Video]

Lecture 34 (Dec 01): Membrane Dynamics

Lecture 35 (Dec 03): Membrane Protein Folding & Self-Assembly

Lecture 36 (Dec 06): Ion Channels: Permeation & Gating

Lecture 37 (Dec 08): Direct & Secondary Active Transport


Problem Sets, Prior Exams & Answers

Proteins: Problem Set 01 [PDF] Answers [PDF]

Proteins: Problem Set 02 [PDF] Answers [PDF]

Proteins: Problem Set 03 [PDF] Answers [PDF]

Proteins: Problem Set 04 [PDF] Answers [PDF]

Proteins Module Exam (2017) [PDF] Answers [PDF]

Proteins Module Exam (2018) [PDF] Answers [PDF]

Proteins Module Exam (2019) [PDF] Answers [PDF]

Proteins Module Exam (2021) [PDF] Answers [PDF]

Nucleic Acids Module Exam (2017) [PDF] Answers [PDF]

Nucleic Acids Module Exam (2018) [PDF] Answers [PDF]

Nucleic Acids Module Exam (2019) [PDF] Answers [PDF]

Nucleic Acids Module Exam (2021) [PDF] Answers [PDF]

Glycobiology & Membrane Proteins Module Exam (2018) [PDF] Answers [PDF]

Glycobiology & Membrane Proteins Module Exam (2019) [PDF] Answers [PDF]


Discussion Sections

Discussion 01 (Sep 02): How to Use VMD, Chimera and PyMOL [Video-Fall2020]

Discussion 02 (Sep 09): Tertiary Alphabet for the Observed Protein
Structural Universe, C. O. Mackenzie, J. Zhou and G. Grigoryan,
Proceedings of the National Academy of Sciences USA, E7438-E7447 (2016) [PDF]

A useful summary of the above PNAS article appeared at Phys.org as:
Managing Compleity: Novel Protein Folding Tool Vastly Simplifies
Understanding How Sequence Encodes Structure, S. M. Dambrot, (2016) [PDF]

Note, a recent, related article is: Universal Architectural Concepts
Underlying Protein Folding Patterns, A. S. Konagurthu, R. Subramanian,
L. Allison, D. Abramson, P. J. Stuckey, M. Garcia de la Banda
and A. M. Lesk, Frontiers in Molecular Biosciences, 7, 612920 (2021) [PDF]

Discussion 03 (Sep 16): Ultrafast Folding Kinetics of WW Domains
Reveal How the Amino Acid Sequence Determines the Speed Limit to Protein
Folding, M. Szczepaniak, M. Iglesias-Bexiga, M. Cerminara, M. Sadqi,
C. Sanchez de Medina, J. C. Martinez, I. Luque and V. Munoz, Proceedings
of the National Academy of Sciences USA, 116, 8137-8142 (2019) [PDF]

A review of the folding mechanism of fast folding proteins by some
of the same authors is: When Fast is Better: Protein Folding Fundamentals
and Mechanisms From Ultrafast Approaches, V. Munoz and M. Cerminara,
Biochemical Journal, 473, 2545-2559 (2016) [PDF]

Discussion 04 (Sep 23): Effective Concentrations Enforced
by Disordered Linkers are Governed by Polymer Physics,
C. S. Sorensen and M. Kjaerjaard, Proceedings of the National
Academy of Sciences USA, 116, 8137-8142 (2019) [PDF]

Discussion 05 (Sep 30): Protein-Peptide Association
Kinetics Beyond the Seconds Timescale from Atomistic Simulations,
F. Paul, C. Wehmeyer, E. T. Abualrous, H. Wu, M. D. Crabtree,
J. Schoneberg, J. Clarke, C. Freund, T. R. Weikl and F. Noe,
Nature Communications, 8, 1095-1104 (2017) [PDF]

Discussion 06 (Oct 07): Conformational Ensembles of an
Intrinsically Disordered Protein Consistent with NMR, SAXS, and
Single-Molecule FRET, G.-N. Gomes, M. Krzeminski, A. Namini, E. W. Martin,
T. Mittag, T. Head-Gordon, J. D. Forman-Kay and C. C. Gradinaru,
Journal of the American Chemical Society, 142, 15697-15710 (2020) [PDF]

Discussion 07 (Oct 14): A Guanine-Flipping and Sequestration
Mechanism for G-Quadruplex Unwinding by Rec Helicases,
A. F. Voter, Y. Qiu, R. Tippana, S. Myong and J. L. Keck,
Nature Communications, 9, 4201-4208 (2018) [PDF]

Discussion 08 (Oct 21): A Single-Molecule Visualisation of DNA
G-Quadruplex Formation in Live Cells, M. Di Antonio, A. Ponjavic,
A. Radzevicius, R. T. Ranasinghe, M. Catalano, X. Zhang, J. Shen,
L.-M. Needham, S. F. Lee, D. Klenerman and S. Balasubramanian,
Nature Chemistry, 12, 832-837 (2020) [PDF]

Discussion 09 (Oct 28): Make-up Lecture by Prof. Hall, due to
BBSB Retreat at the St. Louis Zoo during class on Friday, October 29th

Discussion 10 (Nov 04): Structural Basis for Regulation of
METTL16, an S-Adenosylmethionine Homeostasis Factor, K. A. Doxtader,
P. Wang, A. N Scarborough, D. Seo, N. K. Conrad and Y. Nam,
Molecular Cell, 71, 1001-1011 (2018) [PDF]

Discussion 11 (Nov 11): An Intrinsic Mechansim of Secreted
Protein Aging and Turnover, W. H. Yang, P. V. Aziz, D. M. Heithoff,
M. J. Mahan, J. W. Smith and J. D. Marth,
Proc. Natl. Acad. Sci. USA, 112, 13657-13662 (2015) [PDF]

Discussion 12 (Nov 18): Small RNAs are Modified with N-Glycans
and Displayed on the Surface of Living Cells, R. A. Flynn, K. Pedram,
S. A. Malaker, P. J. Batista, B. A. H. Smith, A. G. Johnson, B. M. George,
K. Majzoub, P. W. Villalta, J. E. Carette and C. R Bertozzi,
Cell, 184, 3109-3124 (2021) [PDF]

Discussion 13 (Dec 02): The Fluid Mosaic Model of the
Structure of Cell Membranes, S. J. Singer and G. L. Nicolson,
Science, 175, 720-731 (1972) [PDF]


Reading Materials & References

Protein Structure & Taxonomy

Proteins Are Polymers that Fold into Specific Structures, Chapter 1, Protein Actions,
I. Behar, R. L. Jernigan and K. A. Dill, pg. 1-28, Garland Science (2017) [PDF]

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]

Interesting Web Sites for Protein Structural Analysis [PDF]

Protein Folding & Stability

Proteins Have Stable Equilibrium Conformations, Chapter 3, Protein Actions,
I. Behar, R. L. Jernigan and K. A. Dill, pg. 53-80, Garland Science (2017) [PDF]

Folding and Aggregration Are Cooperative Transitions, Chapter 5, Protein Actions,
I. Behar, R. L. Jernigan and K. A. Dill, pg. 107-128, Garland Science (2017) [PDF]

The Principles of Protein Folding Kinetics, Chapter 6, Protein Actions,
I. Behar, R. L. Jernigan and K. A. Dill, pg. 129-160, Garland Science (2017) [PDF]

The Protein Folding Problem, 50 Years On,
K. A. Dill and J. L. McCallum, Science, 338, 1042-1046 (2012) [PDF]

When Fast is Better: Protein Folding Fundamentals and Mechanisms
from Ultrafast Approaches, V. Munoz and M. Cerminara,
Biochemical Journal, 473, 2545-2559 (2016) [PDF]

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]

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]

The Protein Folding Problem, K. A. Dill, S. B. Ozkan, M. S. Shell and
T. R. Weikl, Annual Reviews of Biophysics, 37, 289-316 (2008) [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]

Intrinsically Disordered Protein Regions

The Functional Importance of Structure in Unstructured Protein Regions,
N. E. Davey, Current Opinion in Structural Biology, 56, 155-163 (2019) [PDF]

Intrinsically Disordered Proteins and Their "Mysterious" (Meta)Physics,
V. N. Uversky, Frontiers in Physics, 7, 10 (2019) [PDF]

Intrinsically Disordered Protein Regions and Phase Separation:
Sequence Determinants of Assembly or Lack Thereof, E. W. Martin and
A. S. Holehouse, Emerging Topics in Life Sciences, 4, 307-329 (2020) [PDF]

Molecular Dynamics & Monte Carlo Simulation

Molecular Simulations and Conformational Sampling, Chapter 10, Protein Actions,
I. Behar, R. L. Jernigan and K. A. Dill, pg. 221-249, Garland Science (2017) [PDF]

Protein Design & Structure Prediction

The Coming Age of de Novo Protein Design, P.-S. Huang,
S. E. Boyken and D. Baker, Nature, 537, 320-327 (2016) [PDF]

Accurate Prediction of Protein Structures and Interactions Using a
Three-Track Neural Network, M. Baek, F. DiMaio, I. Anishchenko,
J. Dauparas, S. Ovchinnikov, G. R. Lee, J. Wang, Q. Cong, L. N. Kinch,
R. D. Schaeffer, C. Millan, H. Park, C. Adams, C. R. Glassman,
A. DeGiovanni, J. H. Pereira, A. V. Rodrigues, A. A. van Dijk,
A. C. Ebrecht, D. J. Opperman, T. Sagmeister, C. Buhlheller,
T. Pavkov-Keller, M. K. Rathinaswamy, Udit Dalwadi, C. K. Yip, J. E. Burke,
K. C. Garcia, N. V. Grishin, P. D. Adams, R. J. Read and D. Baker,
Science, 373, 871-876 (2021) [PDF]

DeepMind's AlphaFold 2

CASP14: What Google DeepMind's AlphaFold2 Really Achieved,
and What It Means for Protein Folding, Biology and Bioinformatics,
C. O. Rubiera, Oxford Protein Informatics Group, December 2020 [PDF]

Protein Structure Prediction Revolutionized, M. AlQuraishi,
Nature, 596, 487-488 (2021) [PDF]

Highly Accurate Protein Structure Prediction with AlphaFold,
J. Jumper, R. Evans, A. Pritzel, T. Green, M. Figurnov, O. Ronneberger,
K. Tunyasuvunakool, R. Bates, A. Zidek, A. Potapenko, A. Bridgland,
C. Meyer, S. A. A. Kohl, A. J. Ballard, A. Cowie, B. Romera-Paredes,
S. Nikolov, R. Jain, J. Adler, T. Back, S. Petersen, D. Reiman,
E. Clancy, M. Zielinski, M. Steinegger, M. Pacholska, T. Berghammer,
S. Bodenstein, D. Silver, O. Vinyals, A. W. Senior, K. Kavukcuoglu,
P. Kohli and D. Hassabis, Nature, 596, 583-589 (2021) [PDF]

Highly Accurate Protein Structure Prediction for the Human Proteome,
K. Tunyasuvunakool, J. Adler, Z. Wu, T. Green, M. Zielinski, A. Žídek,
A. Bridgland, A. Cowie, C. Meyer, A. Laydon, S. Velankar, G. J. Kleywegt,
A. Bateman, R. Evans, A. Pritzel, M. Figurnov, O. Ronneberger, R. Bates,
S. A. A. Kohl, A. Potapenko, A. J. Ballard, B. Romera-Paredes,
S. Nikolov, R. Jain, E. Clancy, D. Reiman, S. Petersen, A. W. Senior,
K. Kavukcuoglu, E. Birney, P. Kohli, J. Jumper and D. Hassabis
Nature, 596, 590-596 (2021) [PDF]

Using AI to Accelerate Scientific Discovery,
John Kendrew Lecture, Part 1, by Demis Hassabis, DeepMind,
October 2021, MRC Laboratory of Molecular Biology, Cambridge, UK [MP4]

Highly Accurate Protein Structure Prediction with AlphaFold,
John Kendrew Lecture, Part 2, by John Jumper, DeepMind,
October 2021, MRC Laboratory of Molecular Biology, Cambridge, UK [MP4]

Polymer Statistics

Ideal Chains, Chapter 2, Polymer Physics, M. Rubinstein
and R. H. Colby, Oxford University Press, 2003, [PDF]

Real Chains, Chapter 3, Polymer Physics, M. Rubinstein
and R. H. Colby, Oxford University Press, 2003, [PDF]

Thermodynamics of Mixing, Chapter 4, Polymer Physics,
M. Rubinstein and R. H. Colby, Oxford University Press, 2003, [PDF]

Nucleic Acid Structure & Folding

Tutorial on Base Pairing, John Taylor, Chemistry, Washington University [PDF]

Online Book on Nucleic Acid Structure, Chemistry & Biophysics,
Chapters 1-6 and 9, John Taylor, Chemistry, Washington University [PDF]

Symmetry in Nucleic-Acid Double Helices,
U. Heinemann and Y. Roske, Symmetry, 17, 737 (2020) [PDF]

The Thermodynamics of DNA Structural Motifs, J. SantaLucia, Jr. and D. Hicks,
Annual Reviews of Biophys & Biomol Structure, 33, 415-440 (2004) [PDF]

Conformation Changes of Non-B DNA, J. Choi and T. Majima,
Chemical Society Reviews, 40, 5893-5909 (2011) [PDF]

RNA Structural Biology

Geometric Nomenclature and Classification of RNA Base Pairs,
N. B. Leontis and E. Westhof, RNA, 7, 499-512 (2001) [PDF]

The Molecular Interactions That Stabilize RNA Tertiary Structure:
RNA Motifs, Patterns, and Networks, S. E. Butcher and A. M. Pyle,
Accounts of Chemical Research, 44, 1302-1311 (2011) [PDF]

Secondary Structural Model of Human MALAT1 Reveals Multiple Structure-
Function Relationships, P. J. McCown, M. C. Wang, L. Jaeger and J. A. Brown,
International Journal of Molecular Sciences, 20, 5610 (2019) [PDF]

RNA Editing Race Intensifies as Big Pharma Buys In, R. Cross,
Chemical & Engineering News, October 23, 2021 [PDF]

Electron Microscopy / Cryo-EM

How Cryo-EM is Revolutionizing Structural Biology,
X.-C. Bai, G. McMullan and S. H. W. Scheres,
Trends in Biochemical Sciences, 40, 49-57 (2015) [PDF]

Cryo-EM: A Unique Tool for the Visualization of Macromolecular Complexity,
E. Nogales and S. H. W. Scheres, Molecular Cell, 58, 677-689 (2015) [PDF]

Developments, Applications, and Prospects of Cryo-Electron Microscopy,
X. Benjin and L. Ling, Protein Science, 29, 872-882 (2020) [PDF]

MRC LMB Cryo-Electron Microscopy Short-Course (2017)
First Intro Lecture by Richard Henderson, 2017 Nobel Prize Winner [MP4]
Link to the full set of 10 course lectures posted on YouTube [YouTube]

Glycobiology

Essentials of Glycobiology, 3rd Edition,
edited by A. Varki, et al., CHS Press, 2017 [EBook]

Biological Roles of Glycans, Glycobiology, 27, 3-49 (2017) [PDF]

Glycobiology Simplified: Diverse Roles of Glycan
Recognition in Inflammation, R. L. Schnaar,
Journal of Leukocyte Biology, 99, 1-14 (2016) [PDF]

How Glycobiology Can Help Us Treat and Beat the COVID-19 Pandemic,
R. D. Lardone, Y. C. Garay, P. Parodi, S. de la Fuente,
G. Angeloni, E. O. Bravo, A. K. Schmider and F. J. Irazoqui,
Journal of Biological Chemistry, 296, 100375 (2021) [PDF]

Membranes & Membrane Proteins

The Lipid Bilayer Membrane and its Protein Constituents,
J. L. Robertson, Journal of General Physiology, 150, 1472-1483 (2018) [PDF]

Membrane Lipids: Where They Are and How They Behave,
G. van Meer, D. R. Voelker and G. W. Feigenson,
Nature Reviews Molecular Cell Biology, 9, 112-124 (2008) [PDF]

Understanding the Diversity of Membrane Lipid Composition,
T. Harayama and H. Reizman,
Nature Reviews Molecular Cell Biology, 19, 281-296 (2018) [PDF]

Membranes by the Numbers, R. Phillips, Chapter 3 from
Physics of Biological Membranes, P. Bassereau and P. Sens, Eds.,
Springer International Publishing, 2018, [PDF]


Molecular Modeling Software

Software Information [TEXT]

Chimera [DIR]

ChimeraX [DIR]

KiNG [DIR]

PyMOL [DIR]

VMD [DIR]