MODULES | SCHEDULE | Canvas | Molecular Interactions | Flash Cards | Amino Acids Cheat Sheet | Text: Lehninger | Sample Quizzes | PyMol Site License | Zip Extract | Biochemistry Periodic Table | GA Tech Software | Pymol ATP_synthase | Structures | Williams | Origins of Life |

Course Description: This course covers principles of protein, nucleic acid, carbohydrate and lipid structure, assembly, and function. Topics include detailed descriptions of three-dimensional structures and mechanisms, in the context of molecular interactions. Students learn to understand, visualize and analyze large biological assemblies in three dimensions. The course is intended to meet the needs of undergraduate students who are contemplating graduate school, medical school, physician assistant programs, pharmacy school, and/or the universe.

Class structure: Canvas, email, Piazza and the course homepage (here) will be used for exchanging information. Students are expected to attend each lecture unless there is a compelling, approved reason to miss. Students are expected to check their email, engage on Piazza, monitor the course homepage, and the course Canvas page on a frequent basis. Each unexcused absence accrues a 1% grade average penalty.

Grades: Grades are determined by problem sets, quizes, a final exam, and participation in class and office hours. A Problem Set is worth 10 points (390 pts total). A quiz is 40 points (400 pts total). The final exam is 300 pts (75% of the final exam will be very similar to material covered on the quizes. 25% of the exam will cover general material from course lectures). Participation counts for 100 points and is determined by oral contributions in class, questions and answers on Piazza, and discussions at office hours. Extra credit might be offered, at the discretion of the professor. To obtain a letter grade of A, a student must obtain greater than 90%. To obtain a letter grade of B, a student must obtain greater than 80%.

To receive credit for a problem set, it must be correct, complete, on-time, and organized. Problem sets are posted below under Modules. Quiz and exam dates are posted below on the Schedule. Problem sets are due at midnight of the date assigned. Problem set due dates are fixed and are not negotiable under any circumstances. Late problem sets are docked 20% per day.

Lecture Format: Some class sessions will be conventional lectures and others will be inverted, so that students can work together and with the instructor to complete problem sets.

Textbook: The textbook for this couse is Lehninger Principles of Biochemistry, Seventh Edition. This edition is several years old and is free (Biochemistry does not change so fast).

Required Software: PyMol and Endnote. Instructions for downloading and installing PyMol are found in Problem Sets 1 and 2.

Instructor:
Loren Williams
Office: 1309 IBB (at Tech)
Office hours: Immediately after class at Frankfurt de la Vila or by appointment.

TA:
Izaro Sánchez Azcarate

Email: When sending an e-mail message, please put the following information in the subject line:
CHEM 3521, firstname lastname, subject
Example:
CHEM 3521, Christiani Renaldo, I am the center of the universe

Honor Code: In this class we will adhere to the Georgia Tech Honor Code. However, students are allowed to collaborate on problem sets and should feel free to work together. Plagiarism is not allowed. Each student must compile and write-up their own work.

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Supplementary Materials:

• Branden and Tooze, Introduction to Protein Structure, Second Edition, Garland Publishing, 1999.
• R.D. Blake, Informational Biopolymers of Genes and Gene Expression, University Science Books, 2005
• Voet and Voet, Biochemistry, John Wiley & Sons, Inc.
• Jane Richardson's Anatomy of Protein Structure
• Library of Pymol Scripts, List of Pymol Commands.

Background Protein Literature

TOP | Molecular Interactions | Williams

1. Williams, L. "Molecular Interactions", [web site] [short range repulsion PyMol script; water PyMol script; CG base pairing PyMol script; ATP-Mg²⁺ PyMol script]
2. Runnels, C., Lanier, K.A., Williams, J.K., Bowman, J.C., and Williams, L.D. "The Essential Nature of Biopolymers", J. Mol. Evolution, 86, pgs 598–610(2018) [paper] [DNA PyMol script, RNA PyMol script peptide PyMol script cellulose PyMol script].
3. Ramachandran, G.N., Ramakrishnan, C., and Sasisekharan, V. "Stereochemistry of Polypeptide Chain Configurations", J. Mol. Biol. 7, 95-99 (1963) [paper] [peptide bond PyMol script; φ/ψ PyMol script] [biography of Ramachandran]
4. Pauling, L., Corey, R.B., and Branson, H.R. "The Structure of Proteins - 2 Hydrogen-Bonded Helical Configurations of the Polypeptide Chain", Proc. Natl. Acad. Sci. U.S.A. 37, 205-211 (1951) [Pauling 1951 α-helix paper] [α-helix PyMol script] [Pauling 1951 β-sheet paper paper] [antiparallel β-sheet PyMol script; parallel β-sheet PyMol script] [biography of Pauling, biography of Corey] [background papers by Dunitz 2001, Eisenberg 2003]
5. Kyte, J., and Doolittle, R.F. "A Simple Method for Displaying the Hydropathic Character of a Protein", J. Mol. Biol. 157, pgs 105-132 (1982) [paper] [hydropathy Web Server].
6. Vojtěchovský, J., Chu, K., Berendzen, J., Sweet, R.M. and Schlichting, I., "Crystal structures of myoglobin-ligand complexes at near-atomic resolution", Biophysical Journal, 77 pgs 2153-2174 (1999) [paper] [myoglobin PyMol script] [Kendrew's paper; biography of Kendrew; biography of Dorothy Crowfoot Hodgkins]
7. Anfinsen, C.B., Haber, E., Sela, M., and White, F.H., Jr. "The Kinetics of Formation of Native Ribonuclease During Oxidation of the Reduced Polypeptide Chain", Proc. Natl. Acad. Sci. U.S.A. 47, pgs 1309-1314 (1961) [paper] [ribonuclease A PyMol script] [info on ribonuclease] [biography of Anfinsen] [background paper by Levinthal] [background papers by Onuchic & Wolynes 2004, Karplus 1997, Honig 1999, Williams, 2018, Eisenberg on Lisa Steiner]
8. Kovacs, N.A., Petrov, A.S., Lanier, K.A., and Williams, L.D. "Frozen in Time: The History of Proteins", Mol. Biol. Evol. 34, pgs 1252–1260 (2017) [paper] [PyMol script] [background papers by Dill and Lupas].
9. Levitt, M., and Chothia, C. "Structural Patterns in Globular Proteins", Nature 261, 552-558 (1976) [paper] [protein domain PyMol script] [background papers by Shultz & Schirmer 1974 and Levitt]
10. Knowles, T.P., Vendruscolo, M., and Dobson, C.M. "The Amyloid State and Its Association with Protein Misfolding Diseases", Nature reviews. Molecular cell biology 15, pgs 384 (2014) [paper] [Nowick paper] [PyMol script for Dobson paper] [PyMol script for Nowick paper] [PyMol script for Nowick paper] [Eisenberg 2007] [Prusiner 1998, Eisenberg 2005]
11. Buller, A.R., and Townsend, C.A. "Intrinsic Evolutionary Constraints on Protease Structure, Enzyme Acylation, and the Identity of the Catalytic Triad", Proc. Natl. Acad. Sci. U.S.A. 110, E653-E661 (2013) [paper] [PyMol script] [Serine Protease Mechanism Powerpoint]
12. Saibil, H.R., Fenton, W.A., Clare, D.K., and Horwich, A.L. "Structure and Allostery of the Chaperonin Groel", J. Mol. Biol. 425, 1476-1487 (2013) [paper] [PyMol script] [Videos 1A, 1B, 2, 3 4]
13. Tompa, P. "Intrinsically Disordered Proteins: A 10-Year Recap", Trends Biochem. Sci. 37, 509-516 (2012) [paper] [Dunker Slides].

    Background Nucleic Acids Literature

    TOP | Molecular Interactions | Williams

14. Watson, J.D., and Crick, F.H. "Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid.", Nature 171, 737-738 (1953) [paper] [PyMol script] [Franklin Paper, 1953; background on Franklin] [How to draw base pairs] [Race for the Double Helix pt 1 / Race for the Double Helix pt 2] ]
15. Hoogsteen, K. "Crystal and Molecular Structure of a Hydrogen-Bonded Complex between 1-Methylthymine and 9-Methyladenine", Acta Crystallographica 16, 907-916 (1963) [paper] [PyMol script] [background paper by Leontis and Westhof]
16. Davis, J.T. "G‐Quartets 40 Years Later: From 5′‐GMP to Molecular Biology and Supramolecular Chemistry", Angewandte Chemie International Edition 43, pgs 668-698 (2004) [paper] [background paper by Davies] [PyMol script]
17. Kim, S.H., Suddath, F.L., Quigley, G.J., McPherson, A., Sussman, J.L., Wang, A.H., Seeman, N.C., and Rich, A. "Three-Dimensional Tertiary Structure of Yeast Phenylalanine Transfer RNA", Science 185, 435-440 (1974) [paper] [PyMol script] [tRNA video] [1974 New Scientist, 1974 letters; Rich to Crick, Aug 9 | Crick to Rich, Sept 4 | Rich to Crick, Oct 11 | Crick to Rich, Oct 22]
18. Mohan, S., Hsiao, C., Bowman, J.C., Wartell, R., and Williams, L.D. "RNA Tetraloop Folding Reveals Tension between Backbone Restraints and Molecular Interactions", J. Am. Chem. Soc. 132, pgs 12679-12689 (2010) [paper] [GNRA tetraloop Pymol Script] [20 Superimposed GNRA Tetraloops]
    18a. Yakovchuk, P., Protozanova, E., and Frank-Kamenetskii, M.D. "Base-Stacking and Base-Pairing Contributions into Thermal Stability of the DNA Double Helix", Nucleic Acids Res. 34, pgs 564-574 (2006) [paper] [Background paper by Privalov] [PyMol script]
19. Jain, A., and Vale, R.D. "RNA Phase Transitions in Repeat Expansion Disorders", Nature (2017) [paper].
20. Simonovic, M., and Steitz, T.A. "A Structural View on the Mechanism of the Ribosome-Catalyzed Peptide Bond Formation", Biochim. Biophys. Acta 1789, 612–623 (2009) [paper] [PyMol script / codon chart / video 1 / video 2 3:40]
21. Liu, X., Bushnell, D.A., and Kornberg, R.D. "RNA Polymerase II Transcription: Structure and Mechanism", Biochimica et Biophysica Acta-Gene Regulatory Mechanisms 1829, 2-8 (2013) [paper] [PyMol script ][powerpoint]
22. Jiang F, Zhou K, Ma L, Gressel S, and Doudna J.A. "Structural Biology. A Cas9-guide RNA complex preorganized for target DNA recognition", Science 348, 1477-1481 (2015) [paper] [Lander Paper] [PyMol script]
23. Yan, C., Hang, J., Wan, R., Huang, M., Wong, C.C., and Shi, Y. "Structure of a Yeast Spliceosome at 3.6-Angstrom Resolution", Science 349, pgs 1182-1191 (2015) [paper].