- March 2: Paul, Aaron
- March 16: Christine, Joe, Tian
- March 23: Grace, Scarlett
- March 30: Meredith, Abinaya, Becky
- April 6: Sara, Dennis, Hunter
- April 13: Emily, Alex, Abby
- April 20: Shamitha, Brennan, Vikram
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Tues, Jan. 26
Presenting: Bruce Donald.
Introductions and Administration
A Brief Introduction to Computational Structural Biology and Drug Design
[Get started]
[Slides (PDF)]
[Zoom Recording]The Textbook for this class is: Algorithms in Structural Molecular Biology (MIT Press, 2011), abbreviated as ASMB.
Order on Amazon. -
Tues, Feb. 2.
Presenting: Bruce Donald.
Topic: Dead-End Elimination and Protein Design: Full Sequence Design
Dear Students,
For every class,
before class starts, please do all the reading, including Supplementary Materials and Footnotes.*
If you don't you will be lost.
Be sure to also do the secondary, background, and "Also Read" assignments.
*Why? See, for example, footnotes 8, 19, and 30 in the [assigned reading] below.- Assignment --- Due Noon Monday
Write three questions you would like answered, or comments you would like discussed, about the assigned reading material below.
Post your questions on Piazza by the deadline.
Answer at least one question posed by someone else.[Slides (PDF)]
[Zoom Recording]
Primary Reading:
Dahiyat and Mayo. De Novo Protein Design: Fully Automated Sequence Selection. Science 278, 82-87 (1997). [PDF]
The Textbook for this class is: Algorithms in Structural Molecular Biology (MIT Press, 2011), abbreviated as ASMB.
Order on Amazon.
Also read:
ASMB Chapter 11 (Algorithms in Structural Molecular Biology (MIT Press, 2011)). [PDF]
PDB id 1FSD, Full sequence design 1 (FSD-1) of beta beta alpha motif, NMR Stucture
And please try to read:
ASMB Chapter 12 (Algorithms in Structural Molecular Biology (MIT Press, 2011)).Here are two helpul videos:
- Force field comparison: Amber, GROMOS, CHARMM, OPLS (see also COMMENTS section)
- Force Field Parameterization
Background Reading: ASMB Chapters 10 and 9.
Hint: you will find the Mayo paper above much easier to read if you read the ASMB textbook chapter 11 first. -
Tue Feb. 9
Presenting: Bruce Donald
Topic: Introduction to Biomolecular NMR for Protein Structure and Dynamics
- Assignment --- Due Monday at Noon
Write three questions you would like answered, or comments you would like discussed, about the assigned reading material below.
Post your questions on Piazza by the deadline.
Answer at least one question posed by someone else.[Zoom Recording]
[Slides part 1 (PDF)]
[Slides part 2 (PDF)]
useful video: [Fourier Transform, Fourier Series, and frequency spectrum]Primary Reading:
ASMB: Chapters 1-5, 8, and 13.
Structure calculation of biological macromolecules from NMR data, by Peter Guntert
A brief introduction to NMR spectroscopy of proteins, by Flemming Poulsen
NMR studies of protein structure and dynamics, by Lewis Kay. -
Tue Feb. 16
Presenting: Bruce Donald
Topic: RDCs and Structure Calculation
Assignment --- Due Monday at Noon
Write three questions you would like answered, or comments you would like discussed, about the assigned reading material below.
Post your questions on Piazza:
Answer at least one question posed by someone else.[Zoom recording]
Primary Reading:
ASMB: Chapters 15-18, 5.
ASMB: Chapters 4,13.
Residual Dipolar Couplings in Structure Determination of Biomolecules, by James Prestegard
Residual Dipolar Couplings: Measurements and Applications to Biomolecular Studies, by Lincong Wang
Secondary reading:
Lecture Notes in Computational Structural Biology- Volume II (LCSB-II) -- draft 2017, Chapter 16.
Try LibProtNMR - Library for Protein NMR.
LibProtNMR is a software platform and library of algorithms in structural molecular biology, and has many computational methods in Biomolecular NMR. -
Tue Feb. 23
Presenting: Bruce Donald
Topic: Protein Design Algorithms
Assignment --- Due Monday at Noon
Write three questions you would like answered, or comments you would like discussed, about the assigned reading material below.
Post your questions on Piazza:
Answer at least one question posed by someone else. The question can be from this week, or last week.[Slides]
Primary Reading:
ASMB Chapter 12, Review chapter 11.
Algorithms for protein design, by Gainza et al.
The Minimized Dead-End Elimination Criterion and Its Application to Protein Redesign in a Hybrid Scoring and Search Algorithm for Computing Partition Functions over Molecular Ensembles, by Georgiev et al.
Secondary reading:
Lecture Notes in Computational Structural Biology- Volume II (LCSB-II) -- draft 2017, Chapters 3,14.
Computational structure-based redesign of enzyme activity, by Chen et al. [PDF]
Computational Design of a PDZ Domain Peptide Inhibitor that Rescues CFTR Activity, by Roberts et al. [HTML, PDF]
Video: Molecular Dynamics Simulation of self assembling Peptide
(from: An amyloid inhibitor octapeptide forms amyloid type fibrous aggregates and affects microtubule motility *)
*You do not have to read this paper before class.Additional Reading:
Leach A R, Lemon A P. Exploring the conformational space of protein side chains using dead-end elimination and the A* algorithm[J]. Proteins Structure Function and Genetics, 1998, 33(2): 227-239. [PDF]
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Tue Mar. 2
Presenting: Paul S., Aaron M.
Topic: SARS-CoV-2 Structure and Inhibitor Design
Assignment --- Due Monday at Noon
Write three questions you would like answered, or comments you would like discussed, about the assigned reading material below.
Post your questions on Piazza:
Answer at least one question posed by someone else. The question can be from this week, or last week.Primary Reading for Paul's Presentation:
Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19, by Huang, Y., Yang, C., Xu, Xf. et al.
Slides for Paul's Presentation: [pptx]
Notes for Paul's Presentation: [pdf]
Primary Reading for Aaron's Presentation:
De novo design of picomolar SARS-CoV-2 miniprotein inhibitors, by Cao, L. et al.
Slides for Aaron's Presentation: [pptx] -
Tuesday - Wednesday, March 9 - 10 : No classes held
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Tue Mar. 16
Presenting: Christine Y., Joe C., Tian Y.
Topic: Machine Learning, Protein Structure, and Drug Discovery
Assignment --- Due Monday at Noon
Write three questions you would like answered, or comments you would like discussed, about the assigned reading material below.
Post your questions on Piazza:
Answer at least one question posed by someone else. The question can be from this week, or last week.[Zoom recording] Primary Reading for Christine's Presentation:
Positive multistate protein design, by Vulcinic, J. et al.
Slides for Christine's Presentation: [pptx]
Notes for Christine's Presentation: [pdf]
Primary Reading for Joe's Presentation:
Distance-based protein folding powered by deep learning, by Xu, J.
Analysis of distance-based protein structure prediction by deep learning in CASP13, by Xu, J., Wang, S.
Slides for Joe's Presentation: [pdf]
Primary Reading for Tian's Presentation:
Identifying the macromolecular targets of de novo-designed chemical entities through self-organizing map consensus, by Reker, D. et al.
Slides for Tian's Presentation: [pptx]
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Tue Mar. 23
Presenting: Grace T., Scarlett X.
Topic: SARS-CoV-2 Inhibitors and the Structural Basis of Specificity
Assignment --- Due Monday at Noon
Write three questions you would like answered, or comments you would like discussed, about the assigned reading material below.
Post your questions on Piazza:
Answer at least one question posed by someone else. The question can be from this week, or last week.[Zoom recording]
Primary Reading for Grace's Presentation:
Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2, by Yan, R. et al.
Slides for Grace's Presentation: [pdf]
Primary Reading for Scarlett's Presentation:
Making the invisible enemy visible, by Richardson, J. et al.
Slides for Scarlett's Presentation: [pdf]
Notes for Scarlett's Presentation: [pdf]
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Tue Mar. 30
Presenting: Meredith B., Abinaya L., Becky A.
Topic: Protein Binding and Unfolding, Molecular Caging, and SARS-CoV-2 Virulance Mutations
Assignment --- Due Monday at Noon
Write three questions you would like answered, or comments you would like discussed, about the assigned reading material below.
Post your questions on Piazza:
Answer at least one question posed by someone else. The question can be from this week, or last week.Primary Reading for Meredith's Presentation:
Markov State Modeling Reveals Alternative Unbinding Pathways for Peptide-MHC Complexes, by Kavraki, L. et al.
Slides for Meredith's Presentation: [pdf]
Primary Reading for Abinaya's Presentation:
A Robotics-Inspired Screening Algorithm for Molecular Caging Prediction, by Kravchenko, O. et al.
Slides for Abinaya's Presentation: [pptx]
Primary Reading for Becky's Presentation:
D614G mutation alters SARS-CoV-2 spike conformational dynamics and protease cleavage susceptibility at the S1/S2 junction, by Gobeil, S. et al.
Slides for Becky's Presentation: [pdf]
Notes for Becky's Presentation: [pdf]
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Tue Apr. 6
Presenting: Sara B., Dennis H., Hunter S.
Topic: Linear Progamming, Dynamic Programming, and Machine Learning for Provable Protein Design Algorithms
Assignment --- Due Monday at Noon
Write three questions you would like answered, or comments you would like discussed, about the assigned reading material below.
Post your questions on Piazza:
Answer at least one question posed by someone else. The question can be from this week, or last week.Primary Reading for Sara's Presentation:
NMR Assignment through Linear Programming, by Singer, A. et al.
Notes for Sara's Presentation: [pdf]
Primary Reading for Dennis' Presentation:
BWM*: A Novel, Provable, Ensemble-based Dynamic Programming Algorithm for Sparse Approximations of Computational Protein Design, by Jou, J. et al.
Slides for Dennis's Presentation: [pptx]
Primary Reading for Hunter's Presentation:
LUTE (Local Unpruned Tuple Expansion): Accurate Continuously Flexible Protein Design with General Energy Functions and Rigid Rotamer-Like Efficiency, by Hallen, M.A. et al.
Slides for Hunter's Presentation: [pptx]
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Tue Apr. 13
Presenting: Emily C., Alex B., Abby F.
Topic: COVID Fusion Inhibitors, COVID Spike Mutations, and Spike-Binding COVID Antibodies
Assignment --- Due Monday at Noon
Write three questions you would like answered, or comments you would like discussed, about the assigned reading material below.
Post your questions on Piazza:
Answer at least one question posed by someone else. The question can be from this week, or last week.Primary Reading for Emily's Presentation:
Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion, by Xia, S. et al.
Secondary Reading for Emily's Presentation:
Science Magazine Article
Slides for Emily's Presentation: [pdf]
Notes for Emily's Presentation: [pdf]
Primary Reading for Alex's Presentation:
Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity ofthe COVID-19 Virus, by Korber, B. et al.
Slides for Alex's Presentation: [pptx]
Slides for Alex's Presentation: [pdf]
Primary Reading for Abby's Presentation:
Designer antibodies could battle COVID-19 before vaccines arrive, by Cohen, J.
Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies, by Barnes, C.O. et al.
Slides for Abby's Presentation: [pptx]
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Tue Apr. 20
Presenting: Shamitha S., Brennan S., Vikram A.
Topic: COVID Antibodies, ACE2 Binding, and Deep Learning
Last day of class.
All course projects are due today, before the start of class.Please fill out course evaluations on Dukehub.
Assignment --- Due Monday at Noon
Write three questions you would like answered, or comments you would like discussed, about the assigned reading material below.
Post your questions on Piazza:
Answer at least one question posed by someone else. The question can be from this week, or last week.Primary Reading for Shamitha's Presentation:
Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms, by Tortorici, M.A. et al.
Slides for Shamitha's Presentation: [pptx]
Primary Reading for Brennan's Presentation:
Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding, by Starr, T.N. et al.
Slides for Brennan's Presentation: [pptx]
Notes for Brennan's Presentation: [pdf]
Primary Reading for Vikram's Presentation:
Design of proteins presenting discontinuous functional sites using deep learning, by Tischer, D. et al.
Slides for Vikram's Presentation: [pptx]
Notes for Vikram's Presentation: [pdf]
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For each class, I assign primary reading (journal papers) which are the main thing
to present. Background and introductory material is given in the textbook chapters
to help you present. Do not present this textbook chapter material or write course notes about it,
unless it is necessary for understanding the main papers.
Piazza website
for this class.
Please check this webpage, and schedule frequently, since I will post new papers and new readings and new assignments frequently, as we proceed through the term.
Please note: These dates and times might move some (see "The Queue", below), as we adapt to the time required to discuss the papers, or if I am unexpectedly called to Washington, etc.
NOTE: To accomodate all the talks this semester, some presenters may be asked to present on the same day. Keep checking the schedule for updates.
Student presentations will proceed in a strict rotation, ordered as a queue. The queue order is:These are not necessarily exact dates but a presentation ordering with estimated dates. This means that if you're planning ahead, your presentation might be moved to the next class, if our discussion takes longer. It will not be possible to plan to give your presentation on a precise day for this reason. However, the order of the presentations should be relatively stable, and, in general you will not be asked to present earlier than the order dictated by the queue. Moreover, in general, the paper you are presenting will be determined well ahead of time so you can prepare.
Because of the complexities of scheduling I cannot accommodate requests to move your presentation. No exceptions will be made for (e.g.) interviews, conferences, family trips, ballet classes, sports events.
*Papers that are not available online (below) have been handed out on paper.
*RECOMB papers (Proceedings of the Nth Annual International Conference on Computational Molecular Biology (N=1,2,3,4,...)) are available online via the ACM Digital Library.
A few papers will be handed out in class. If you miss class, you can copy them from a classmate.
The Textbook for this class is: Algorithms in Structural Molecular
Biology (MIT Press, 2011), abbreviated
as ASMB.
Order
on Amazon.
Other
book sellers
Announcements will be made in class. I will try to post them here, so consult this website.
Class Schedule
NOTE: Some PDF links may only work when accessed while on
Duke's network, or by using the VPN!
NOTE: Zoom recordings and Zoom Live Classes require you to be
authenticated and logged in through Duke.
We will not have a final exam in this class. During the slot for the final, we will have project Presentations from 9-12AM (there will Slides and a presentation , by all students)
here
here and
here is the schedule of papers we read in 2020, 2019, 2018, 2016, 2015, and 2013. We will read different papers this year!
Only one class meeting will have the same papers, and that one class meeting is a warm up.
2020 Schedule (To give you an idea:)
2019 Schedule (To give you an idea:)
2016 Schedule (To give you an idea:)