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]


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


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]


Reading Materials & References

Protein Structure & Taxonomy

Proteins Are Polymers that Fold into Specific Structures, Chapter 1, Protein Actions,

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]

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]

Polymer Statistics

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

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

Polymer Physics, M. Rubinstein and R. H. Colby,
Oxford University Press, 2003, Chapter 4, Ideal Chains [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]

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]


Molecular Modeling Software

Software Information [TEXT]

Chimera [DIR]

ChimeraX [DIR]

KiNG [DIR]

PyMOL [DIR]

VMD [DIR]