Class links
Course Schedule | Canvas | Molecular Interactions | Flash Cards | Biochemistry Periodic Table | Amino Acids | Text: Lehninger | Sample Quizzes | Pymol ATP_synthase | Structures | Project Table | Elements of Loren's Style | Williams |

Tools
GA Tech Software | PyMol | Blender | Molprobity | Clustal Omega | NCBI | UniProt | Human Protein Atlas | PDB | Kegg | AlphaFold | ChatGPT | Google Scholar | Proteovision | Enzyme Commission |

Course Description: This course covers principles of protein, nucleic acid, carbohydrate and lipid structure, assembly, and function. This lecture-based, project-focused course examines one or more macromolecular targets selected by each student in alignment with their graduate research program. The course is tuned to meet the individual needs of students in analyzing and visualizing large biological structures in their research. Through readings, demonstrations, and guided computational exercises, students will learn the conceptual principles and workflows of macromoleculear production and purification, computational analysis and manipulation across multiple platforms, and will develop expertise at multiscale visualizations.

Background Knowledge: Students are expected learn and know the chemical structures on the Course Flashcards and molecular interactions as described on the Molecular Interactions page. Links to these resources are provided at top of this document.

Comunication and Interaction: Canvas, email, Piazza and the course homepage (here) will be important for exchanging information. Students are invited to meet weekly at office hours (coffee provided by the professor) at coffee shops nearby to Tech. The PI's office is also an option.

Student Obligations: Students are expected to attend each lecture unless there is a compelling reason to miss. Students are expected to check their email, monitor the course syllabus, Piazza and the course Canvas page. Deliverables by students include a portfolio of publication-quality figures within a concise written report.

Grades: This course is intended to be safe, informative, helpful, and fun. There are no exams. Grades are determined by quizes (4 of them), problem sets, a final course project, attendance and Piazza participation. The project is due at the final lecture. To receive a grade of A, a student must produce a satisfactory work product and obtain 90% average on the quizes, problem sets, and attendance.

Project: Each student will identify a protein or RNA or polysaccharide or structural lipid, or a multicompoent assembly (virus, ribosome, etc) that is especially relevant to their research. Students should identify and communicate to the professor the name, pdb entry code, and resolution of their target structure Project Table (linked at the top of this page) within the first week of the semester.

Textbook: There is no official textbook. Students must have access to a book that is roughly equivalent to Lehninger Principles of Biochemistry, Seventh Edition. The sections assigned from Lehninger can be found in any standard biochemistry text.

Required Software: PyMol, Endnote, Adobe Creative Suite, ChemDraw, Alphafold, ChatGPT...

Instructor: Professor Loren Williams

Office: Room 1309 IBB

Lectures: The class sessions will be a mixture of conventional and inverted lectures. Students will work together and with the instructor on developing their projects.

Email: loren.williams@chemistry.gatech.edu

When sending an e-mail message, please put the following information in the subject line:
CHEM 6572, firstname lastname, subject

Example: CHEM 6572, Marie Curie, request for radiation badge.

TA None

Time and Place: 11 AM - 11:50 AM MWF, CULC 129

Accomodation: If you require special accommodation we will work with you. Please contact the ADAPTS office and the professor.

Honor Code: In this class we will adhere to the Georgia Tech Honor Code.

Schedule

TOP | Molecular Interactions | Williams

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.ppt]
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 ][ppt]
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].