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CHEM 4511/6501
Biochemistry I: Macromolecular Structure
Spring 2022

under revision 1/21/2022

Schedule | Canvas | Molecular Interactions | Williams | Structures | Pymol ATP_synthase |

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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, or other allied programs.

Class structure: For the first two weeks the class will be virtual. After the first two weeks of the semester, the class will be conducted in-person, in the classroom. However, because some students are more comfortable maintaining 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 physically attend class. Many sessions will be inverted, although there will also be more conventional lectures. The inverted sessions 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.

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, and the course Canvas page on a daily basis. If conditions permit, 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.

Grades: This course is intended to be safe, informative, helpful, and fun. There are no exams. Grades are determined by assignments, quizes, and an optional course project. To receive credit for an assignment, it must be complete, on-time, and organized. A quiz is weighted as an assignment but is graded. Assignment and quiz dates are posted on the schedule. Assignments are due at midnight of the due date. Assignment due dates are fixed and are not negotiable under any circumstances

To receive a letter grade of B, a student must appropriately complete all the assignments. To receive a letter grade of A, a student must appropriately complete all the assignments, do well on the quizes and complete the optional project. This is one of the few classes that you will take at Tech were you are totally and explicitly in control of your grade.

Project: For the optional project a student will independently perform a variety of functional and structural analyses of an assigned enzyme. Specific instructions for the Optional Project are given on the course schedule (see last day of class).

COVID. The first two weeks of the class will be online only. I have been exposed to omicron and I don't want to expose you. After the first two weeks the class revert to in-person, with an option for remote participation. The expectation is that all students will wear masks in the classroom. For specific Georgia Tech policies related to COVID-19, please refer to this site and this site

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

Lecture Format: Some class sessions will be conventional lectures but most 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 4511, firstname lastname, subject
Examples:
CHEM 4511, Marie Curie, request for radiation badge.
CHEM 6501, Mo Salah, request for transfer to Sheffield Wednesday.

TA: Vahab Rajaei, vrajaei3@gatech.edu
(If you send an email to Dr. Williams, please cc it to Vahab, unless there is a specific reason not to.)

Time and Place: 9:30 AM - 11:00 AM Tues, Thurs in Howey Physics L4, 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, private Bluejeans meetings can be arranged, 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. However, students are allowed to collaborate on assignments and should feel free to work together.


TOP

Topics Date
- Topic # 1
Course Intro
Review of Course Syllabus
Biotech Timeline Powerpoint
Intro to Pymol
Intro to Molecular Interactions
Mol Int Reading Assignment (Section A)
Molecular Interactions Powerpoint

Problem Set 1 due

week 1
Tues, 1-11
- Topic # 2
Molecular Interactions: Short Range Repulsion
Mol Int Intro Video
Short Range Repulsion Video
Mol Int Reading Assignment (Section B)
Short Range Repulsion PyMol

Problem Set 2 due

Topic # 3
Molecular Interactions: Electrostatic Interactions
Electrostatic Interactions Video
Mol Int Reading Assignment (Section C)

Problem Set 3 due

week 1
Thurs, 1-13
-
- Topic # 4
Molecular Interactions: Dipolar Interactions
Dipolar Interactions Video
Dispersive Interactions Video
Cation-P video
Mol Int Reading Assignment (Sections D, E, F)

Problem Set 4 due

week 2
Tues, 1-18
- Topic # 5
Molecular Interactions: Hydrogen Bonding
Hydrogen Bonding Interactions Video
Mol Int Reading Assignment (Sections G, H1-H5)
Water Hydrogen Bonding PyMol
Base Pairing Pymol

Problem Set 5 due

Topic # 6
Molecular Interactions: the Hydrophobic Effect
Mol Int Reading Assignment (Sections H6, H7, H8)

Problem Set 6 due

week 2
Thurs, 1-20
-
- Topic # 7
The PDB
PBD Web Site
Protein Assignments
Lehninger: Box 4-4 (8th Ed: Box 4-3)
How to Use the PDB PDF

Problem Set 7 due

week 3
Tues, 1-25
- Topic # 8
PyMol
Pymol Template

Problem Set 8 due

week 3
Thurs, 1-27
-
- Topic # 9
The Peptide Bond
Lehninger: Sections 3.1, 3.2, 3.4, 4.1
Protein Structure Powerpoint
How to draw a peptide video
Peptide Bond Pymol

Problem Set 9 due

Topic # 10
Amino Acids
AA Powerpoint
United States of Amino Acids
AA Flash Cards
AA Venn Diagram
Hydropathy Plot
Sequence Searching Powerpoint

Problem Set 10 due

week 4
Tues, 2-1
- Topic # 11
Torsion Angles φ and ψ
φ / ψ images
1eve φψ map image
Jane Richardson's Molprobity
Make a φψ map with Molprobity
Torsion Pymol

Quiz 1

Problem Set 11 due

week 4
Thurs, 2-3
-
- Topic # 12
Protein Secondary Structure
Lehninger: Section 4.2
α-Helix Pymol
Helical Wheel Generator
anti-parallel β-Sheet Pymol
parallel β-Sheet Pymol
β-turn Pymol

Problem Set 12 due

week 5
Tues, 2-8
- Topic # 13
Protein Tertiary and Quaternary Structure, Intrinsically Disordered Proteins, Fibrous Proteins
Lehninger: Section 4.3 (8th Ed.: Sections 4.3 and 4.5)
Coiled-Coil
Coiled-Coil Builder
Protein Folds Pymol
Albumin Pymol
Porin Pymol
TIM Barrel
 TLR Pymol
Parallel β-helix Pymol

Problem Set 13 due

Topic # 14
Web Tools
General Databases
PDB
Enzyme Commission
AlphaFold
NCBI
Kegg
UniProt
BioNumbers
Classification Databases
ECOD
SCOP
Pfam
Toolkits
MPI Bioinformatics Toolkit
Clustal
Proteovision
EXPASY
EBI

Problem Set 14 due

week 5
Thurs, 2-10
-
- Topic # 15
Protein Folding
Lehninger Section 4.4
Protein Topology Diagram

Problem Set 15 due

week 6
Tues, 2-15
- Topic # 16
Ligand Binding; Myoglobin and Hemoglobin
Lehninger Section 5.1
Myoglobin PyMol
Hemoglobin PyMol

Problem Set 16 due

Topic # 17
Intrinsic Disorder
Intrinsic Disorder Pymol Script

Problem Set 17 due

week 6
Thurs, 2-17
-
- Topic # 18
Enzymes
Lehninger: Section 6.1, 6.2
Enzyme ppt
SwissProt

Quiz 2

Problem Set 18 due

week 7
Tues, 2-22
- Topic # 19
Serine Proteases, Hexokinase
Lehninger: Section 6.4
Serine Protease Powerpoint
Serine Protease gif
Serine Protease Pymol
Hexokinase Pymol

Problem Set 19 due

Topic # 20
Enzyme Kinetics
Lehninger: Section 6.3, Box 6-1 (8th Ed: Section 6.3)
Enzyme Kinetics ppt
kcat and Km

Problem Set 20 due

week 7
Thurs, 2-24
-
- Topic # 21
Regulatory Enzymes
Lehninger: Section 6.5
Phosphfructokinase Pymol

Problem Set 21 due

week 8
Tues, 3-1
- Topic # 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

Problem Set 22 due

week 8
Thurs, 3-3
- -
- Topic # 23
Motors, continued
Myosin
G Johnson Video
Myosin Pymol Script
Microtube Motors
Kinesin
Ron Vale Kinesin
Dynein
Ron Vale Dynein

Problem Set 23 due

week 9
Tues, 3-8
- Topic # 24
Motors, continued
ATP Synthase
V-ATPase Pymol Script
ATP Synthase GIFs
ATP Synthese Video 1
ATP Synthase Video 2

Problem Set 24 due

Topic # 25
Mono and Di saccharides
Lehninger: Section 7.1
Saccharide ppt
Monosaccharide and Disaccharide Pymol

Problem Set 25 due

week 9
Thurs, 3-10
-
- Topic # 26
Polysaccharides
Cellulose Pymol
Cellulose
Amylose Pymol
Amylose
Glycogen Pymol
Insulin Resistance
Polysaccharide Builder
Lehninger: Section 7.2
assignment 18; in progress

Quiz 3

Problem Set 26 due

week 10
Tues, 3-15
- Topic # 27
Glycoconjugates
Lehninger: Section 7.3
glycosylated Spike

Problem Set 27 due

week 10
Thurs, 3-17
- -
- Spring Break holiday
week 11
Tues, 3-22
- Spring Break holiday
week 11
Thurs, 3-24
- -
- Topic # 28
Bases, Nucleosides and Nucleotides
Lehninger Section 8.1
Nucleic Acid Powerpoint
How to draw a base pair
ATP Pymol

Problem Set 28 due

week 12
Tues, 3-29
- Topic # 29
DNA and RNA Structure #1
DNA Pymol

Problem Set 29 due

week 12
Thurs, 3-31
- -
- Topic # 30
DNA and RNA Structure #2
Lehninger Section 8.2
Hoogsteen Pymol
syn/anti Pymol
Proteovision

Quiz 4

Problem Set 30 due

week 13
Tues, 4-5
- Topic # 31
Nucleic Acid Chemistry, Nucleotide Function
Lehninger: Section 8.3, 8.4
RNA Pymol
tRNA Pymol
GNRA Tetraloop Pymol
GNRA Tetraloop Diversity Pymol

Problem Set 31 due

week 13
Thurs, 4-7
-
- Topic # 32
Genes and Gene Products
Lehninger: Section 9.1

Problem Set 32 due

Topic # 33
DNA-Based Methods to Understand Protein Function
Lehninger: Section 9.2
Back Translate
PCR cloning
Calculate Reverse Complement
NEB Find a Restiction Enzyme
SNAPGene

Problem Set 33 due

week 14
Tues, 4-12
- Topic # 34
Lipids
Lehninger Section 10.1, 10.2
lipid ppt
Membrane Pymol

Problem Set 34 due

Topic # 35
The Composition and Architecture of Membranes
Lehninger Section 11.1
assignment 26, in progress

Problem Set 35 due

week 14
Thurs, 4-15
-
Topic # 36
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

Problem Set 36 due

week 15
Tues, 4-19
- Topic # 37
Transcription
Lehninger Section 26.1
Transcription ppt
RNA Polymerase Pymol
TBP Pymol

Problem Set 37 due


week 15
Thurs, 4-21
-
- Topic # 38
Translation
Lehninger Section 27.1, 27.2
Translation ppt1
Translation ppt2
tRNA Pymol
Glutamyl-tRNA sythetase Pymol
Ribosome Pymol

Problem Set 38 due

week 16
Tues, 4-26
last class
Final Project Due: Mon, 5-2, midnight
- --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].