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CHEM 6572
Macromolecular Structure
Fall 2021

under revision 11/03/2021

Schedule | Canvas | AA flash cards | Molecular Interactions | Williams | Structures | Pymol ATP_synthase |

class recordings | 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 | 35JR | 36 | 37 | 38 Timeline | 39 | 40 | 42 | 43 | 44 | 45 | 46 |


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 tuned to meet the needs of graduate students who require background and tools for analyzing large biological structures in their research.

Class structure: This class will be conducted in-person, in the classroom. However, because some students are more comfortable maintaining social distance, all class activities will be available in real time online, and will be recorded and posted. Therefore, it is not necessary for students to attend class. Many classes will be inverted, although there will also be more conventional lectures. The inverted lectures are intended for the professor to assist students with their assignments.

Bluejeans, Canvas and the course homepage (here) will be used for exchanging information and for broadcasting the lectures online.

Subsets of the class will 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 be optional. For specific Georgia Tech policies related to COVID-19, please refer to this site and this site.

Students are expected to attend each lecture, either in-person or online, unless there is a compelling reason to miss. Students are expected to check their email, monitor the course syllabus, email and the course Canvas page on a daily basis.

Grades: This course is intended to be safe, informative, helpful, and fun. There are no exams. Grades are determined by assignments, presentations and a final course project. To receive credit for an assignment, it must be complete, on-time, and organized. Assignments are posted in the schedule and are due at midnight of their due date. Assignment due dates are fixed and are not negotiable under any circumstances. A project is due on the last day of the semester.

To receive a letter grade of A, a student must appropriately complete all the assignments, the course project, and the presentation. Due dates for assignments are listed on the course schedule. There are over 30 assignments - nearly one for every lecture. Each student will present important aspects of their protein/RNA to the class, using PyMol. Powerpoint will not be used for presentations.

Project: Each student will identify a protein or RNA that is especially relevant to their research. Each student will independently perform a variety of functional and structural analysis on their protein or RNA. Students should identify and communicate to the professor the name, pdb entry code, and resolution of their protein/RNA by lecture 6.

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 and Endnote- available from OIT

Instructor: Professor Loren Williams

Office: Room 1309 IBB

Lectures: Some class sessions will be conventional lectures but most sessions will be inverted, so that students can work together and with the instructor to complete assignments.

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, Cherry Emerson 204, or Bluejeans.

Office hours: I will remain on Bluejeans after every class for as long as anyone wants to talk with me. For less public interactions, specific Bluejeans meetings can be set up. I can meet with students upon request.


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

Topics Date
------------ Lecture # 1
Course Intro
Intro to Pymol
Intro to Molecular Interactions
Molecular Interactions pdf
lecture 1
week 1
Mon, 8-23
------------ Lecture # 2
Molecular Interactions
Mol Int Intro Video
Short Range Repulsion Video
Short Range Repulsion PyMol
assignment 1 due
lecture 2
week 1
Wed, 8-25
------------ Lecture # 3
Molecular Interactions
Electrostatic Interactions Video
Mol Int Reading Assignment (Sects A, B, C)
assignment 2 due
lecture 3
week 1
Friday, 8-27
------------ ------------ ------------
------------ Lecture # 4
Molecular Interactions
Dipolar Interactions Video
Dispersive Interactions Video
Cation-P video
Mol Int Reading Assignment (Sections D, E, F)
assignment 3 due
lecture 4
week 2
Mon, 8-30
------------ Lecture # 5
Molecular Interactions
Hydrogen Bonding Interactions Video
Mol Int Reading Assignment (Sections G, H)
Water Hydrogen Bonding PyMol
Base Pairing Pymol
assignment 4 due

lecture 5
week 2
Wed, 9-1
------------ Lecture # 6
Hydrophobic Effect
assignment 5 due
assignment 5a due
lecture 6
week 2
Fri, 9-3
------------ ------------ ------------
------------ Labor Day Holiday
week 3
Mon, 9-6
------------ Lecture # 7
The PDB
PBD
Lehninger: Box 4-4
How to Use the PDB
lecture 7
week 3
Wed, 9-8
------------ Lecture # 8
PyMol
assignment 5b due
Pymol Template
lecture 8
week 3
Fri, 9-10
------------ ------------ ------------
------------ Lecture # 9
The Peptide Bond
Lehninger: Sections 3.1, 3.2, 3.4, 4.1
Protein Structure Powerpoint
How to draw a peptide
Peptide Bond Pymol
Sequence Searching
assignment 6 due
lecture 9
week 4
Mon, 9-13
------------ Lecture # 10
Amino Acids
AA Powerpoint
AA Flash Cards
AA Venn Diagram
Hydropathy Plot
lecture 10
week 4
Wed, 9-15
------------ Lecture # 11
assignment 7 due
lecture 11
week 4
Fri, 9-17
------------ ------------ ------------
------------ Lecture # 12
Protein Secondary Structure
Lehninger: Section 4.2
φ / ψ
1eve φψ map
Torsion Pymol
α-Helix Pymol
Helical Wheel Generator
anti-parallel β-Sheet Pymol
parallel β-Sheet Pymol
β-turn Pymol
Jane Richardson's Molprobity
Make a φψ map with Molprobity
assignment 8 due
assignment 8a due
lecture 12
week 5
Mon, 9-20
------------ Lecture # 13
Protein Tertiary and Quaternary Structure, Intrinsically Disordered Proteins, Fibrous Proteins
Lehninger: Section 4.3
Coiled-Coil
Coiled-Coil Builder
Protein Folds Pymol
Albumin Pymol
Porin Pymol
TIM Barrel
 TLR
Parallel β-helix
Ribosome Pymol
lecture 13
week 5
Wed, 9-22
------------ Lecture # 14
Web Tools
General Databases
PDB
AlphaFold
NCBI
Klegg
UniProt
Classification Databases
ECOD
SCOP
Pfam
Toolkits
MPI Bioinformatics Toolkit
Proteovision
EXPASY
EBI
assignment 9 due
lecture 14
week 5
Fri, 9-24
------------ ------------ ------------
------------ Lecture # 15
Protein Folding
Lehninger Section 4.4
Protein Topology Diagram
assignment 10 due
lecture 15
week 6
Mon, 9-27
------------ Lecture # 16
Ligand Binding; Myoglobin and Hemoglobin
Lehninger Section 5.1
Myoglobin PyMol
Hemoglobin PyMol
lecture 16
week 6
Wed, 9-29
------------ Lecture # 17
Intrinsic Disorder
Intrinsic Disorder Pymol Script
assignment 11 due
lecture 17
week 6
Fri, 10-1
------------ ------------ ------------
------------ Lecture # 18
Enzymes
Lehninger: Section 6.1, 6.2
Enzyme ppt
SwissProt
assignment 12 due
lecture 18
week 7
Mon, 10-4
------------ Lecture # 19
Serine Proteases, Hexokinase
Lehninger: Section 6.4
Serine Protease Powerpoint
Serine Protease Pymol
Hexokinase Pymol
lecture 19
week 7
Wed, 10-6
------------ Lecture # 20
Enzyme Kinetics
Lehninger: Section 6.3 and Box 6-1
Enzyme Kinetics ppt
kcat and Km
assignment 13 due
lecture 20
week 7
fri, 10-8
------------ ------------ ------------
------------ Fall Break holiday
week 8
Mon, 10-11
------------ Lecture # 21
Regulatory Enzymes
Lehninger: Section 6.5
Phosphfructokinase Pymol
assignment 14 due
lecture 21
week 8
Wed, 10-13
------------ Lecture # 22
Motors and Translocases
Lehninger Section 5.3
ATP and Mechano-chemical coupling
Actin
Motors Powerpoint
Cytokinesis: Chromatid Translocation
Actin Treadmilling
Actin Pymol
Ron Vale: Molecular Motors
lecture 22
week 8
Fri, 10-15
------------ ------------ ------------
------------ Lecture # 23
Motors, continued
Myosin
G Johnson Video
Myosin Pymol Script
Microtube Motors
Kinesin
Ron Vale Kinesin
Dynein
Ron Vale Dynein
assignment 15 due
lecture 23
week 9
Mon, 10-18
------------ Lecture # 24
Motors, continued
ATP Synthase
V-ATPase Pymol Script
ATP Synthase GIFs
ATP Synthese Video 1
ATP Synthase Video 2
assignment 16 due
lecture 24
week 9
Wed, 10-20
------------ Lecture # 25
Mono and Di saccharides
Lehninger: Section 7.1
Saccharide ppt
Monosaccharide and Disaccharide Pymol
assignment 17 due
lecture 25
week 9
Fri, 10-22
------------ ------------ ------------
Lecture # 27
student PyMol presentations
lecture 26
week 10
Mon, 10-25
Lecture # 26
student PyMol presentations
lecture 27
week 10
Wed, 10-27
------------ Lecture # 28
Polysaccharides
Cellulose Pymol
Cellulose
Amylose Pymol
Amylose
Glycogen Pymol
Insulin Resistance
Polysaccharide Builder
Lehninger: Section 7.2
assignment 18; in progress
lecture 28
week 10
Fri, 10-29
------------ ------------ ------------
------------ Lecture # 29
Glycoconjugates
Lehninger: Section 7.3
glycosylated Spike
assignment 19 due
lecture 29
week 11
Mon, 11-1
------------ Lecture # 30
Bases, Nucleosides and Nucleotides
Lehninger Section 8.1
Nucleic Acid Powerpoint
How to draw a base pair
ATP Pymol
lecture 30
week 11
Wed, 11-3
------------ Lecture # 31
DNA Pymol
assignment 20 due
lecture 31
week 11
Fri, 11-5
------------ ------------ ------------
------------ Lecture # 32
DNA and RNA Structure
Lehninger Section 8.2
Hoogsteen Pymol
syn/anti Pymol
Proteovision
assignment 21 due
lecture 32
week 12
Mon, 11-8
------------ Lecture # 33
Nucleic Acid Chemistry, Nucleotide Function
Lehninger: Section 8.3, 8.4
RNA Pymol
tRNA Pymol
GNRA Tetraloop Pymol
GNRA Tetraloop Diversity Pymol
assignment 22 due
lecture 33
week 12
Wed, 11-10
------------ Lecture # 34
RNA World ppt
lecture 34
week 12
Fri, 11-12
------------ ------------ ------------
------------ Lecture # 35
Jane Richardson Visit
lecture 35
week 13
Mon, 11-15
------------ Lecture # 36
Genes and Gene Products
Lehninger: Section 9.1
Bam HI Pymol
BGL II Pymol
Eco RI Pymol
Fok I Pymol
Not I Pymol
Pvu II Pymol
Biotechnology Timeline
assignment 23 due
DNA-Based Methods to Understand Protein Function Lehninger: Section 9.2
Back Translate
PCR cloning
Calculate Reverse Complement
NEB Find a Restiction Enzyme
SNAPGene
assignment 24 due
lecture 36
week 13
Wed, 11-17
------------ Lecture # 37
Lipids
Lehninger Section 10.1, 10.2
lipid ppt
Membrane Pymol
assignment 25 due
lecture 37
week 13
Fri, 11-19
------------ ------------ ------------
Lecture # 38
The Composition and Architecture of Membranes
Lehninger Section 11.1
assignment 26, in progress
lecture 38
week 14
Mon, 11-22
------------ ------------
lecture 39
week 14
Wed, 11-24
------------ Thanksgiving Holiday
week 14, Fri, 11-26
------------ ------------ ------------
------------ Lecture # 39
Replication
DNA Replication ppt
Stephen Bell Movie 1
Stephen Bell Movie 2
movie 1a
movie 2a
movie 3a (Fork Coupling)
movie 4a (2:27)
Helicase Movie
Bacillus DNA Polymerase I Pymol Script
assignment 27 due
lecture 40
week 15
Mon, 11-29
------------ Lecture # 40
Transcription
Lehninger Section 26.1
Transcription ppt
RNA Polymerase Pymol
TBP Pymol
lecture 41
week 15
Wed, 12-1
------------ Lecture # 41
Translation
Lehninger Section 27.1, 27.2
Translation ppt1
Translation ppt2
tRNA Pymol
Glutamyl-tRNA sythetase Pymol
Ribosome Pymol
assignment 28 due
lecture 42
week 15
Fri, 12-3
------------ ------------ ------------
Lecture # 42
Final Project Due: 12-16-2021 Midnight
Mon, 12-6
------------ ------------ ------------
------------ --the end--- ------------

Supplementary Materials:


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].