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CHEM 4511/6501
Biochemistry I: Macromolecular Structure
Spring 2023

4/21/2023

TOPICS | SCHEDULE | Canvas | Molecular Interactions | Flash Cards | Williams | Structures | Lehninger | Pymol ATP_synthase | Quizzes


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: Canvas, email and the course homepage (here) will be used for exchanging information. 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, and the course Canvas page on a daily basis. Subsets of the class will meet perodically for coffee hours (coffee provided by the professor) to be conducted at Starbucks, Dancing Goats or Blue Donkey.

Grades: This course is intended to be informative, helpful, and fun. Grades are determined by problem sets, quizes, a final exam and optional course projects. To receive credit for a problem set, it must be correct, complete, on-time, and organized. There are around 40 problem sets. A quiz is weighted as two problem sets. The final exam is weighted as 5 problem sets. Problem sets are posted below on the Topics List. 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. The lowest scoring problem set and the lowest quiz will be dropped.

To receive a letter grade of B, a student must average 80% on the quizes, problem sets and the final exam. To receive a letter grade of A, a student must average 80% on the quizes, problem sets and the final exam and must also complete the optional project.

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).

Textbook: The textbook for this couse is Lehninger Principles of Biochemistry, Seventh Edition. This edition is several years old and is free.

Required Software: PyMol and Endnote - available from OIT. Here is the PyMol License.


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 problem sets.

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.

TAs: Kavita Matange, Christopher Whittington

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.


TOP | TOPICS

Date Lecture Number Topic Number Quiz Quiz Topic / Misc
Tuesday, January 10, 2023 1 1
Thursday, January 12, 2023 2 2
Tuesday, January 17, 2023 3 3,4,5
Thursday, January 19, 2023 4 6,7 A Molecular Interactions
Example Quiz
Tuesday, January 24, 2023 5 8,9
Thursday, January 26, 2023 6 10 Thermo
Tuesday, January 31, 2023 7 10 continued B Problem Set 10 Due
Thursday, February 2, 2023 8 11
Tuesday, February 7, 2023 9 12,13 C Amino Acids / Peptides
Thursday, February 9, 2023 10 14
Tuesday, February 14, 2023 11 15
Thursday, February 16, 2023 12 16,17 D (cancelled) Protein Structure
Tuesday, February 21, 2023 13 18
Thursday, February 23, 2023 14 19,20
Tuesday, February 28, 2023 15 21 E Enzymes
Thursday, March 2, 2023 16 22
Tuesday, March 7, 2023 17 23,24
Thursday, March 9, 2023 18 25
Tuesday, March 14, 2023 19 26 F Sugars
Thursday, March 16, 2023 20 27
Tuesday, March 21, 2023 Spring Break
Thursday, March 23, 2023 Spring Break
Tuesday, March 28, 2023 21 28,29
Thursday, March 30, 2023 22 30,31 G DNA Backbone/Base Pairs
Tuesday, April 4, 2023 23 32
Thursday, April 6, 2023 24 33,34
Tuesday, April 11, 2023 25 35 Lipids / Membranes
Thursday, April 13, 2023 26 36 H
Tuesday, April 18, 2023 27 37
Thursday, April 20, 2023 28 38 I Central Dogma
Tuesday, April 25, 2023 29 38 Last Lecture
Wednesday, April 26 - Tuesday, May 2 Reading Period
Thursday, May 4, 2023 Final
8:00 am - 10:50 am


TOP | SCHEDULE

Topics
- 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

- 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

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

Problem Set 3

- 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

- 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

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

Problem Set 6

- Topic # 7
The First Law,
the Second Law,
the Universe,
and the System (you)

Basic Thermo Powerpoint
Lehninger Sections 13.1, 13.3

Problem Set 7

-
- Topic # 8
The PDB
PBD Web Site
Protein Assignments
Lehninger: Box 4-4 (8th Ed: Box 4-3)
How to Use the PDB PDF

Problem Set 8

- Topic # 9
PyMol
Pymol Template

Problem Set 9

- Topic # 10
The Peptide Bond
Lehninger: Sections 3.1, 3.2, 3.4, 4.1
Levels of Protein Structure Powerpoint
How to draw a peptide video
Example Peptides
Peptide Bond Pymol

Problem Set 10

- Topic # 11
Amino Acids
AA Powerpoint
United States of Amino Acids
AA Flash Cards
AA Flash Cards (quizlet)
AA Venn Diagram
Make a Hydropathy Plot
Sequence Searching Powerpoint

Problem Set 11

- Topic # 12
Torsion Angles φ and ψ
φ / ψ images
Phi Psi Powerpoint
1eve φψ map image
Jane Richardson's Molprobity
Make a φψ map with Molprobity
Torsion Pymol

Problem Set 12

Extra Credit Homework (1)
- Topic # 13
Protein Secondary Structure
Lehninger: Section 4.2
Handedness Powerpoint
Secondary Structure Images
Alpha Helix Powerpoint
α-Helix Pymol
Helical Wheel Generator
Beta Sheet Powerpoint
anti-parallel β-Sheet Pymol
parallel β-Sheet Pymol
β-turn Pymol

Problem Set 13

- Topic # 14
Protein Tertiary and Quaternary Structure, Fibrous Proteins
Lehninger: Section 4.3 (8th Ed.: Sections 4.3 and 4.5)
Globular Proteins Powerpoint
Fibrous Proteins Powerpoint
Coiled-Coil Pymol
Coiled-Coil Builder
Protein Folds Pymol
Albumin Pymol
Porin Pymol
TIM Barrel Pymol
TLR Pymol
Parallel β-helix Pymol
Beta Turn Powerpoint

Problem Set 14

- Topic # 15
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 15

- Topic # 16
Protein Folding
Protein Folding Powerpoint
Lehninger Section 4.4
Protein Topology Diagram

Problem Set 16

- Topic # 17
Intrinsic Disorder
Intrinsic Disorder Powerpoint
Intrinsic Disorder Pymol Script

Problem Set 17

- Topic # 18
Ligand Binding; Myoglobin and Hemoglobin
Lehninger Section 5.1
Myoglobin/Hemoglobin Powerpoint
Myoglobin PyMol
Hemoglobin PyMol

Problem Set 18

- Topic # 19
Enzymes
Lehninger: Sections 6.1, 6.2
Enzyme Powerpoint
Induced Fit: Hexkinase PyMol
Fe-S: Nitrogenase PyMol
SwissProt

Problem Set 19

- Topic # 20
Serine Proteases, Hexokinase
Lehninger: Section 6.4
Serine Protease Powerpoint
Serine Protease gif
Serine Protease PyMol
Sars COV-19 Protease PyMol
Hexokinase Pymol

Problem Set 20

- Topic # 21
Enzyme Kinetics
Lehninger: Section 6.3, Box 6-1 (8th Ed: Section 6.3)
Enzyme Kinetics Powerpoint
kcat and Km

Problem Set 21

- Topic # 22
Biopolymer Manipulation and Characterization
Lehninger: Sections 3.3, 9.1 and 9.2
Biopolymer Powerpoint
Protein Purification Video
Back Translate
PCR cloning
Calculate Reverse Complement
NEB Find a Restiction Enzyme
SNAPGene

Problem Set 22

- Topic # 23
Regulatory Enzymes
Lehninger: Section 6.5
Phosphofructokinase Powerpoint
Phosphofructokinase Pymol

Problem Set 23

-
- Topic # 24
Motors and Translocases
Lehninger: Section 5.3
ATP and Mechano-chemical coupling
Actin
Motors Powerpoint
Cytokinesis: Chromatid Translocation Video
Actin Treadmilling Video
Actin Pymol
Ron Vale: Molecular Motors Video

Motors, continued
Myosin
G Johnson Video
Myosin Pymol Script
Microtube Motors
Kinesin
Ron Vale Kinesin Video
Dynein
Ron Vale Dynein
Motors, continued
ATP Synthase
V-ATPase Pymol Script
ATP Synthase GIFs
ATP Synthese Video 1
ATP Synthase Video 2

Problem Set 24a

Problem Set 24b

Problem Set 24c

- Topic # 25
Mono and Di saccharides
Lehninger: Section 7.1
Monosaccharide Powerpoint
Monosaccharide and Disaccharide Pymol

Problem Set 25

- Topic # 26
Polysaccharides

Polysaccharide Powerpoint
Cellulose Pymol
Cellulose
Amylose Pymol
Amylose
Glycogen Pymol
Insulin Resistance
Polysaccharide Builder
Lehninger: Section 7.2

Problem Set 26

- Topic # 27
Glycoconjugates
Lehninger: Section 7.3
glycosylated Spike

Problem Set 27

- Topic # 28
Bases, Nucleosides and Nucleotides
Lehninger Section 8.1
DNA Powerpoint
RNA Powerpoint
How to draw a base pair Powerpoint
ATP Pymol

Problem Set 28

- Topic # 29
DNA and RNA Structure #1
DNA Pymol

Problem Set 29

- Topic # 30
DNA and RNA Structure #2
Lehninger Section 8.2
Hoogsteen Pymol
syn/anti Pymol
rRNA secondary structures

Problem Set 30

- Topic # 31
Nucleic Acid Chemistry, Nucleotide Function
Lehninger: Sections 8.3, 8.4
RNA Pymol
tRNA Pymol
GNRA Tetraloop Pymol
GNRA Tetraloop Diversity Pymol

Problem Set 31

- Topic # 32
Special Topic
Life Powerpoint

Problem Set 32

- Topic # 33
Endnote
Endnote Tutorial

Problem Set 33

- Topic # 34
Lipids
Lehninger Sections 10.1, 10.2
Lipids Powerpoint
Membranes Powerpoint
Steroids Powerpoint
Membrane Pymol

Problem Set 34

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

Problem Set 35

Topic # 36
Replication
DNA Replication Powerpoint
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

- Topic # 37
Transcription
Lehninger Section 26.1
Transcription Powerpoint
RNA Polymerase Pymol
TBP Pymol

Problem Set 37


- Topic # 38
Translation
Lehninger Section 27.1, 27.2
Translation Powerpoint #1
Translation Powerpoint #2
tRNA Pymol
Glutamyl-tRNA sythetase Pymol
Ribosome Pymol

Problem Set 38


Final Project

- --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 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].