Chemistry & Physics of Biomolecules

Biology 5357

Fall Term 2023

Coursemaster: Jay Ponder


General Information

Syllabus & Schedule [PDF]


Lecture Summaries

Lecture 01 (Aug 28): Protein Taxonomy I: Primary & Secondary Structure [PDF]

Lecture 02 (Aug 30): Protein Taxonomy II: Motifs & Supersecondary Structure [PDF]

Lecture 03 (Sep 01): Protein Taxonomy III: Tertiary Structure & Fold Types [PDF]

Lecture 04 (Sep 06): Forces that Determine Protein Structure [PDF]

Lecture 05 (Sep 08): Theory & Mechanisms of Protein Folding [PDF]

Lecture 06 (Sep 11): Experimental Protein Folding Studies [PDF]

Lecture 07 (Sep 13): Experimental Protein Folding Studies II

Lecture 08 (Sep 18): Introduction to Intrinsically Disordered Proteins [PDF]

Lecture 09 (Sep 20): Tools for Biophysical Characterizationof IDRs [PDF]

Lecture 10 (Sep 22): Biological Functions of IDRs [PDF]

Lecture 11 (Sep 25): Mutagenesis Studies of Folding & Stability [PDF]

Lecture 12 (Sep 27): Neural Networks & DeepMind's AlphaFold [PDF]

Lecture 13 (Oct 02): Polymer Statistics I: Basic Theory [PDF]

Lecture 14 (Oct 04): Polymer Statistics II: Real Chains & Applications [PDF]

Lecture 15 (Oct 06): Polymer Statistics III: Mixtures of Polymers [PDF]

Lecture 16 (Oct 11): DNA, RNA & Their Physico-Chemical Properties [PDF] [MP4]

Lecture 17 (Oct 13): Nucleic Acid Duplex Stability [PDF]

Lecture 18 (Oct 16): RNA Binds Ligands [PDF]

Lecture 19 (Oct 18): Riboswitch Decisions & RNA Interactions [PDF]

Lecture 20 (Oct 20): Dynamics of Tertiary Interactions [PDF]

Lecture 21 (Oct 23): RNA Does Chemistry [PDF]

Lecture 22 (Oct 25): Protein-Nucleic Acid Interactions [PDF]

Lecture 23 (Oct 30): Basic Principles of Electron Microscopy [PDF]

Lecture 24 (Nov 01): Electron Microscopy & Biomolecular Assemblies [PDF]

Lecture 25 (Nov 06): Introduction to Glycobiology [PDF]

Lecture 26 (Nov 08): Glycan Structure & Analysis Methods [PDF]

Lecture 27 (Nov 10): Classes of Glycoproteins & Glycolipids [PDF]

Lecture 28 (Nov 13): Glycans in Cell Signaling & Disease States [PDF] [MP4]

Lecture 29 (Nov 15): Discovery of the Membrane & Embedded Proteins [PDF] [Notes] [MP4]

Lecture 30 (Nov 17): Chemical Composition of the Cell Membrane [PDF] [Notes] [MP4]

Lecture 31 (Nov 20): Membrane Structure & Mechanics [PDF] [Notes] [MP4]

Lecture 32 (Nov 27): Membrane Dynamics [PDF] [Notes] [MP4]

Lecture 33 (Nov 29): Electrical Signaling & Ion Permeation [PDF]

Lecture 34 (Dec 01): Electrical Sensing & Gating [PDF] [MP4]

Lecture 35 (Dec 04): Membrane Protein Folding & Dynamics [PDF]

Lecture 36 (Dec 06): Direct & Secondary Active Transport [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 [PDF]

Proteins Module Exam (2022) [PDF] Answers

Proteins Module Exam (2023) [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]

Nucleic Acids Module Exam (2022) [PDF]

Nucleic Acids Module Exam (2023) [PDF]

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

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

Glycobiology & Membrane Proteins Module Exam (2021) [PDF]

Glycobiology & Membrane Proteins Module Exam (2022) [PDF]

Glycobiology & Membrane Proteins Module Exam (2023) [PDF]


Discussion Sections

Discussion 01 (Aug 31): How to Use Chimera, PyMOL and VMD [Video 2020]

Discussion 02 (Sep 07): A Lysine-Cysteine Redox Switch with an
NOS Bridge Regulates Enzyme Function, M. Wensien, F. Rabe von Pappenheim,
L.-M. Funk, P. Kloskowski, U. Curth, U. Diederichsen, J. Uranga, J. Ye,
P. Fang, K.-T. Pan, H. Urlaub, R. A. Mata, V. Sautner and K. Tittmann,
Nature, 593, 460-468 (2021) [PDF]

Discussion 03 (Sep 21): Mega-Scale Experimental Analysis of
Protein Folding Stability in Biology and Design, K. Tsuboyama, J. Dauparas,
J. Chen, E. Laine, Y. M. Behbahani, J. J. Weinstein, N.M. Mangan,
S. Ovchinnikov and G. J.Rocklin, Nature, 620, 434-444 (2023) [PDF]

Discussion 04 (Sep 28): Extreme Disorder in an Ultrahigh-
Affinity Protein Complex, A. Borgia, M. B. Borgia, K.Bugge,
V. M. Kissling, P. O. Heidarsson, C. B. Fernandes, A. Sottini,
A. Soranno, K. J. Buholzer, D. Nettes, B. B. Kradglund, R. B. Best
and B. Schuler, Nature, 555, 61-66 (2018) [PDF]

Discussion 05 (Oct 05): 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, 23124-23131 (2019) [PDF]

Discussion 06 (Oct 12): Structure-Based Mechanistic Insights
into CNMT1-Mediated Maintenance DNA Methylation, J. Song, M. Teplova,
S. Ishibe-Murakami and D. J. Patel, Science, 335, 709-712 (2012) [PDF]

Discussion 07 (Oct 19): Structure of Human RNase H1 Complexed
with an RNA/DNA Hybrid: Insight into HIV Reverse Transcription,
M. Nowotny, S. A. Gaidamakov, R. Ghirlando, S. M. Cerritello,
R. J. Crouch and W. Yang, Molecular Cell, 28, 264-276 (2007) [PDF]

Discussion 08 (Oct 26): RNA Thermometer Controls Temperature-
Dependent Virulence Factor Expression in Vibrio cholerae,
G. G. Weber, J. Kortmann, F. Narberhaus and K. E. Klose, Proceedings
of the National Academy of Sciences USA, 111, 14241-14246 (2014) [PDF]

Discussion 09 (Nov 09): 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 10 (Nov 16): Cellular Glycan Modification by B3GAT1
Broadly restricts Influenza Virus Infection, J. D. Trimarco, S. L. Nelson,
R. R. Chaparian, A. Il Wells, N. B. Murray, P. Azadi, C. B. Coyne,
and N. S. Heaton, Nature Communications, 13, 6456 (2022) [PDF]

Discussion 11 (Nov 30): The Fluid Mosaic Model of the Structure of Cell
Membranes, S. J. Singer and G. L. Nicolson, Science, 175, 720-731 (1972) [PDF] [Notes]


Reading Materials & References

Protein Structure & Taxonomy

Introduction to Protein Structure, Second Edition,
C. Branden and J. Tooze, Garland Science (1999) [PDF]

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]

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

Extreme Disorder in an Ultrahigh-Affinity Protein Complex, A. Borgia,
M. B. Borgia, K.Bugge, V. M. Kissling, P. O. Heidarsson, C. B. Fernandes,
A. Sottini, A. Soranno, K. J. Buholzer, D. Nettes, B. B. Kradglund,
R. B. Best and B. Schuler, Nature, 555, 61-66 (2018) [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]

The Molecular Basis for Cellular Function of Intrinsically Disordered
Regions, A. S. Holehouse and B. B. Kragelund, manuscript in preparation, [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]

DNA & 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]

Detection of Alternative DNA Structures and Its Implications
for Human Disease, G. Matos-Rodrigues, J. A. Hisey, A. Nussenzweig
and S. M. Mirkin, Molecular Cell, 83, 3622-3641 (2023) [PDF]

Integrating End-to-End Learing with Deep Geometrial Potentials for
ab Initio RNA Structure Prediction, Y. Li, C. Zhang, R. Pearce,
P. L. Freddolino and Y. Zhang, Nature Communications, 14, 5745 (2023) [PDF]

Electron Microscopy / Cryo-EM

CryoEM 101: Online Information & Training [HTTP]

Architecture of the Human Erythrocyte Ankyrin-1 Complex, F. Vallese,
K. Kim, L. Y. Yen, J. D. Johnston, A. J. Noble, T. Cali, and O. B. Clarke,
Nature Structural & Molecular Biology, 29, 706-718 (2022) [PDF]

Structures from Intact Myofibrils Reveal Mechanism of Thin Filiment
Regulation Through Nebulin, Z. Wang, M. Grange, S. Pospich, T. Wagner,
A. L. Kho, Ml Gautel and S. Raunser, Science, 375, 738 (2022) [PDF]

Glycobiology

Essentials of Glycobiology, 4th Edition,
edited by A. Varki, et al., CHS Press, 2022 [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]

Membranes & Membrane Proteins

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

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

Ion Channels

Ion Selectivity and Conductance, Chapter 1 from Textbook
of Ion Channels, Volume 1, A. A. Simon, C. Fan, D. M. Kim,
J. G. McCoy and C. M. Nimigean, pg. 3-19, CRC Press (2023) [PDF]

Voltage-Dependent Gating of Ion Channels, Chapter 2 from Textbook of
Ion Channels, Volume 1, B. Chanda and S. Choudhury, pg. 21-43, CRC Press (2023) [PDF]


Molecular Modeling Software

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Chimera: Extensible Molecular Modeling System

Chimera 1.16 Software for macOS [DMG]

Chimera 1.16 Software for Windows [EXE]

Chimera 1.16 Software for Linux [BIN]

Chimera Introduction [PDF]

Chimera Installation [PDF]

Chimera User's Guide [PDF] [PDF]

Chimera Getting Started [HTTP]

Chimera PDB File Preparation [PDF]

ChimeraX: Next-Generation of Chimera Software

ChimeraX 1.3 Software for macOS [DMG]

ChimeraX 1.3 Software for Windows [EXE]

ChimeraX 1.3 Software for Ubuntu 20.04 Linux [DEB]

ChimeraX 1.3 Software for Ubuntu 18.04 Linux [DEB]

ChimeraX 1.3 Software for RedHat 8 Linux [RPM]

ChimeraX 1.3 Software for RedHat 7 Linux [RPM]

ChimeraX 1.3 Software for Generic Linux [GZIPPED TAR]]

ChimeraX Overview [PDF]

ChimeraX Features [PDF]

ChimeraX Tutorial [PDF]

ChimeraX User's Guide [HTML]

ChimeraX Publication [PDF]

PyMOL: Python-Enhanced Molecular Graphics

PyMOL 1.7.4.5 Software for macOS [DMG]

PyMOL 1.7.4.5 Software for Windows [MSI]

PyMOL 1.7.4.5 Software for Linux [GZIPPED TAR]

PyMOL Quick Reference [PDF]

PyMOL Introduction [PDF]

PyMOL Tutorial [PDF]

PyMOL User's Guide [PDF]

VMD: Visual Molecular Dynamics

VMD 1.9.4 Software for macOS (10.10 thru 10.13) [DMG]

VMD 1.9.4 Software for macOS (10.15, Catalina) [DMG]

VMD 1.9.4 Software for macOS (11, Big Sur, Intel) [DMG]

VMD 1.9.4 Software for macOS (11, Big Sur, Apple M1) [DMG]

VMD 1.9.4 Software for Windows [EXE]

VMD 1.9.4 Software for Linux [GZIPPED TAR]

VMD User's Guide [PDF]

Using VMD Tutorial [PDF]

VMD Tutorial Files [GZIPPED TAR] [ZIP]

KiNG: Interactive Kinemage Viewer

KiNG 2.24 Software for macOS [DMG]

KiNG 2.24 Software for Windows [DMG]

KiNG 2.23 Software for Linux [DMG]

KiNG Installation Guide [PDF]

KiNG Quick Start Guide [PDF]

KiNG User's Guide [PDF]

Kinemage Files for Branden & Tooze [DIR]

Kinemage Tour of Protein Structure Files [DIR]

Kinemage Demonstration Files [DIR]

Kinemage Files for Teaching Proteins [DIR]