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CHEM 6572/4803
Macromolecular Structure
Fall 2020
revised 9/4/2020

Schedule | Assignments | Protein Literature | Nucleic Acid Literature | small molecule flash cards | Alignment |

lecture videos | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | 21 | 22 | 23 | 24 | 25 | 26 | 27 | 28 | 29 | 30 | 31 | 32 | 33 | 34 | 35 |

Course Description: This course covers principles of protein and nucleic acid structure, folding, assembly, stability, dynamics and function. Topics include detailed descriptions of three-dimensional structures, in the context of molecular interactions. Students will learn to visualize and analyze large molecules in three dimensions and to make clear and informative illustrations of complex assemblies.

Special COVID-19 Notes. For specific Georgia Tech policies related to COVID-19, please refer to this site and this site. This graduate level class is offered in the fall of 2020 in a hybrid format. This course will be informal and flexible, and will be tuned to meet the needs of the specific students in the class. Lectures by the professor and student presentations will be conducted on bluejeans. Some pre-recorded videos can be watched at students' convenience. Course reading and background material is posted online. Subsets of the class might meet weekly for in-person discussion coffee hours (coffee provided by the professor) to be conducted in an outdoor venue (locations TBD). These meetings would optional.

Email, Bluejeans chat, and Teams will be used for exchanging information. Grades will be determined by course projects, assignments, presentations and participation in online discussions. There will be no exams. All relevant information is provided in the course syllabus (here) which will be finalized before the first scheduled class period.

You are expected to attend class (online) every session unless you have a compelling reason not to. You are expected to check your email and monitor the course syllabus on a daily basis. This course is intended to be safe, informative, helpful, and fun.

Instructor: Professor Loren Williams

Office: Room 1309 IBB

Lectures: The first three weeks the course will be conducted exclusively online. During the fourth week the presentation mode will be reassessed by the class.

Email: loren.williams@chemistry.gatech.edu (best mode of communication)

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: 11:00 am - 11:50 am MWF, Bluejeans. Klaus 1447 (we probably will not use this space for this course).

Office hours: By appointment. To make an appointment, please contact my administrator, Keisha Harville (keisha.harville@chemistry.gatech.edu). Meetings will be by appointment on Bluejeans.

Course Structure: During this course you will be required (i) to read and understand all of the course literature (links below), (ii) to present various aspects of the course literature to the class, and (iii) to complete a variety of assignments.

Literature: This course will be taught using peer-reviewed literature as source material, rather than a textbook. The papers here and here will form the basis of the class. All of these materials are required reading.

Presentations: Each student will make a series of presentations of papers to the class. Presenting students must have complete mastery of the technical material of their assigned papers. All students are expected to read and understand all of the papers.

Supplementary Materials:

Software: Each student must download and install Pymol on their computer.

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.

Grades: (not applicable during Fall 2020) will be based on assignments and quizzes (50%), and class participation, including presentations and class discussions (50%). All students are expected to participate in class discussions and to not be passive observers. Quizzes will cover assigned reading and class discussions. Quizzes will sometimes be announced in advance but not always.


TOP | Molecular Interactions | Williams

Images: On the dates indicated on the schedule, open the appropriate Pymol script and create several png images (ray 2000x2000) illustrating the specified structure. Email the images to Loren. The subject line of the email should be: CHEM 6572 (or 4803), first-name last-name, Torsion Image (or α-Helix Image, β-Sheet Image, etc).

Pymol Exercises: On the dates indicated on the schedule, email the completed Pymol Exercises to Loren. The subject line of the email should be: CHEM 6572 (or 4803), first-name last-name, Pymol Exercise Number. Useful Pymol commands.

Bioinformatics Toolkit: As outlined in the lecture (video 18 above) and in Claudia's tutorial tutorial, search for sequences in the PDB that are homologous to your protein using HHpred in the MPI bioinformatics toolkit. Select the 10 best, make sure to select unique hits (select only hits with different identifiers). Forward the selected hits to AlignmentViewer (click on View Alignment). The logo plot will show the most conserved positions in the alignment. Copy the input sequences from the input tab and go to PhyML (in the Classification tab). Compute the maximum-likelihood tree of your sequences. The names of the nodes in the final tree correspond to PDB entries (PDBcode_chain) Use the fetch command (or load) to view these in pymol. Inspect the protein structures related to your query. From your inspection, what are the functions of the highly conserved sequences? Where are the insertions?

name="PrLit" 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].
  14. Nucleic Acids Literature

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  15. 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] ]
  16. 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]
  17. 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]
  18. 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]
  19. 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]
  20. Jain, A., and Vale, R.D. "RNA Phase Transitions in Repeat Expansion Disorders", Nature (2017) [paper].
  21. 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]
  22. 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]
  23. 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]
  24. 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].


TOP | Molecular Interactions | Williams

This schedule will be finalized at the end of the first week when we have a reasonably accurate list of students enrolled in the class.

Presentor Topic Date
Professor Course Intro,
Introduction to Pymol
week 1: m, 8-17
Professor Molecular Interactions
Molecular Interactions Powerpoint
Videos A, B, C
Paper 1, Sections A, B, C
Short Range Repulsion Image due
week 1: w, 8-19
Professor Molecular Interactions Videos D, E, F
Paper 1, Sections D, E, F
Hydrogen Bonding Image due
week 1: f, 8-21
------------ ------------ ------------
Professor Molecular Interactions Videos G
Paper 1, Sections G, H
Base Pairing Image due
Pymol Exercise 1 due
week 2: m, 8-24
Professor Coordinate files and the PBD
How to Use the PDB PDF
week 2: w, 8-26
Professor The Peptide Bond
Protein Structure Powerpoint
How to draw a peptide
Peptide Bond Image due
week 2: f, 8-28
------------ ------------ ------------
Professor Amino Acids
AA Powerpoint
AA Flash Cards
AA Venn Diagram
Project Topic Due
week 3: m, 8-31
Professor Essential Nature of Biopolymers (Paper 2)
Evolution and Tinkering
Polymers Powerpoint
week 3: w, 9-02
Professor Ramachandran (Paper 3)
φ / ψ
φψ map
Torsion Image due
Pymol Exercise 2 due
week 3: f, 9-04
------------ ------------ ------------
**Holiday** Labor Day week 4: m, 9-07
Professor Pauling (Paper 4)
Jane Richardson's Molprobity
Make a φψ map with Molprobity
α-Helix Image due
week 4: w, 9-09
Professor β-Sheet Proteins
Protein Folds Powerpoint
β-Sheet Image due
week 4: f, 9-11
------------ ------------ ------------
Professor α-Helix Proteins
Albumin Image due
Sequence Searching
Pymol Exercise 3 due
week 5: m, 9-14
Professor b-sheet proteins
Porin Image due
week 5: w, 9-16
Professor complex folds
Project sequence due
Project hydropathy plot due
week 5: f, 9-18
------------ ------------ ------------
Students 1, 2 & 3 Paper 5
Pymol Exercise 4 due
week 6: m, 9-21
Students 4, 5 & 6 paper 6
Myoglobin Image due
week 6: w, 9-23
Students 7, 8 & 9 paper 7
Ribonuclease A Image due
week 6: f, 9-25
------------ ------------ ------------
Dr. Claudia Alvarez Carreno MSAs
Multiple Sequence Alignment Tutorial
Pymol Exercise 5 due (word doc)
week 7: m, 9-28
Students 10, 11 & 12 paper 8
Ribosome Image due
week 7: w, 9-30
Students 13, 14 & 15 paper 9
Protein Folds Images due
SCOP database
CASP database
Pfam database
week 7: f, 10-02
------------ ------------ ------------
Professor Background week 8: m, 10-05
Students 16, 17 & 18 paper 10
Pymol Exercise 6 due
week 8: w, 10-07
Students 19, 20 & 21 paper 11
Bioinformatics Toolkit Assignment Due
week 8: f, 10-09
------------ ------------ ------------
Professor Enzymes
Serine Protease Powerpoint
Serine Protease Image due
week 9: m, 10-12
Professor Enzymes week 9: w, 10-14
Students 22, 23 & 24 paper 12 week 9: f, 10-16
------------ ------------ ------------
Professor background
Pymol Exercise 7 due
week 10: m, 10-19
Students 1, 4 & 7 paper 13 week 10: w, 10-21
Professor Background week 10: f, 10-23
------------ ------------ ------------
Students 2, 5 & 8 paper 14
Pymol Exercise 8 due
DNA Image due

Draw Base Pairs Powerpoint
week 11: m, 10-26
Professor DNA
Nucleic Acid Powerpoint
week 11: w, 10-28
Students 3, 6 & 9 paper 15
Hoogsteen Image due
week 11: f, 10-30
------------ ------------ ------------
Professor RNA
RNA Image due
week 12: m, 11-02
Students 10, 14 & 17 paper 17
tRNA Image due
week 12: w, 11-04
Professor paper 18
GNRA Tetraloop Image due
Pymol Exercise 8 due
week 12: f, 11-06
------------ ------------ ------------
Students 12, 16 & 19 paper 19 week 13: m, 11-09
Students 13, 17 & 20 paper 20 week 13: w, 11-11
Professor The Ribosome week 13: f, 11-13
------------ ------------ ------------
Professor Conclusion week 14: m, 11-16
------------ --the end--- ------------

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List of Students:

  1. Andrews, Megan Holly
  2. Badilla-Nunez, Kelly Johana
  3. Ehrlich, Samuel Michael
  4. Fu, Yibo
  5. Grant, Arshay Juanisha
  6. Hagwood, Abigail Marie
  7. Hersey, Ashley Nicolle
  8. Huang, Brian David
  9. Jin, Jiangpeiyun
  10. Kay, Valerie Ellen
  11. Kern, Ryan Elliott Birch
  12. Liu, Buyun
  13. Milner, Prasaad Thomas
  14. O'Rourke, Leah Elizabeth
  15. Rajaei, Vahab
  16. Scelsi, Hailee Fay
  17. Singh, Sohaj R
  18. Thomas, Gwendell
  19. Vasudevan, Vaibhav S
  20. Wang, Zeyu
  21. Whalen, Brendan
  22. Wood, Fiona Claire
  23. Xu, Xing