Computer Science 590.01
Topics in Computational Structural Biology

To give you an idea about the class, below please find the schedule from the last seminar, in 2013. We will read entirely different papers this time. Only one class meeting will have the same papers, and that one class meeting is a warm up.

• Schedule for 2013 class

Schedule and Readings

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.

The Queue

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:
We will not assign exact dates to presentations but only an order in which the papers will be presented. 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 N^th 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.
Announcements will be made in class. I will try to post them here, so consult this website.

Here is a useful bibliography of papers (and PDFs) in the area of this course.

NOTE: Some PDF links may only work when accessed while on Duke's network, or by using the VPN!

1. Weds, Jan. 7 North 311
   Presenting: Bruce Donald.
   Introductions and Administration
   

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2. Monday, 1/12 North 311
   Presenting: Bruce Donald.
   Dead-End Elimination and Protein Design: Full Sequence Design
   
   Dear Students,
   For every class,
   Please do all the reading.
   If you don't you will be lost.
   Be sure to also do the secondary, background, and "Also Read" assignments.
   
   Primary Reading:
   Dahiyat, B. I. 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.
   
   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
   And please try to read:
   ASMB Chapter 12 (Algorithms in Structural Molecular Biology (MIT Press, 2011)).
   Background Reading: ASMB Chapters 10 and 9.
   

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3. Monday, 1/19 North 311
   No Class, MLK Holiday
   

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4. Monday, 1/26 North 311
   Presenting: Hunter Nisonoff.
   De novo design of a transmembrane Zn²⁺-transportng four-helix bundle.
   [Slides ppt] [Slides pdf]
   [Notes]
   Primary Reading:
   Joh NH, Wang T, Bhate MP, Acharya R, Wu Y, Grabe M, Hong M, Grigoryan G, DeGrado WF.
   De novo design of a transmembrane Zn²⁺-transporting four-helix bundle. Science 346, 1520-1524 (2014). [PDF]
   Supplementary Materials [PDF]
   
   Also Read:
   Grigoryan G. Absolute free energies of biomolecules from unperturbed ensembles. JCC 34, 2726-2741 (2013). [PDF]
   
   Background Reading:
   Methods in Enzymology: Chapters 2,4,6,8
   ASMB: Chapters 9,10,11,12, 25
   

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5. Monday, 2/2 North 311
   
   
   Assignment:
   Do this quiz, and turn it in on Sakai by 1:00 PM, Feb. 9. Instructions. The quiz is based on the papers and discussion of Sparse Graphs in Protein Design.
   
   Project proposals are due on February 6th. See projects.
   
   We have two presenters today.
   • Sparse Graphs in Protein Design
     Presenting: Swati Jain
     [Slides ppt] [Slides pdf]
     [Astar ppt]
     Primary Reading:
     
     NB: When we say in parentheses, e.g., "(Page 3)" or "Section 5 (Page 10)" we mean that only these pages/sections are necessary to understand the presentation. You should, of course, also read more of the paper if you can.
     Absent such parenthetical restictions, you should read all of the paper with the greatest of attention.
     • Xu J, Berger B. Fast and Accurate Algorithms for Protein Side-Chain Packing. Journal of ACM 53, 533-557 (2006). - (Page 3) [PDF]
       
     • Xu J. Rapid Protein Side-Chain Packing via Tree Decomposition. RECOMB, 423-439 (2005). - Section 2 (Page 3), Section 5 (Page 10) [PDF]
       
     • Leaver-Fay A, Tyka M, Lewis SM, Lange OF, Thompson J, Jacak R, Kaufman K, Renfrew PD, Smith CA, Sheffler W, Davis IW, Cooper S, Treuille A, Mandell DJ, Richter F, Ban YE, Fleishman SJ, Corn JE, Kim DE, Lyskov S, Berrondo M, Mentzer S, Popovic Z, Havranek JJ, Karanicolas J, Das R, Meiler J, Kortemme T, Gray JJ, Kuhlman B, Baker D, Bradley P..
       Rosetta3: An Object-Oriented Software Suite for the Simulation and Design of Macromolecules. Methods in Enzymology 487, 546-574 (2011). - Section 4.6.2 (Page 16), Section 4.6.3 (Page 18), Section 4.6.4 (Page 19) [PDF]
       
     • Kingsford CL, Chazelle B, Singh M. Solving and Analyzing Side-Chain Positioning Problems using Linear and Integer Programming. Bioinformatics 21, 1028-1036 (2004). - Problem Formulation Section (Page 2), Energy Function Section (Page 4) [PDF]
       
     • Canutescu AA, Shelenkov AA, Dunbrack RL Jr. A Graph-Theory Algorithm for Rapid Protein Side-Chain Prediction - Materials and Methods Section. Protein Science 12, 2001-2014 (2003). - (Page 5 only) [PDF]
       
     • Jou JD, Jain S, Georgiev I, Donald BR. BWM^*: A Novel, Provable, Ensemble-based Dynamic Programming Algorithm for Sparse Approximations of Computational Protein Design. RECOMB (2015) Warsaw, Poland. April 12, 2015 (In Press). [PDF]
       
     • Leaver-Fay A, Kuhlman B, Snoeyink J. An Adaptive Dynamic Programming Algorithm for the Side Chain Placement Problem. Pacific Symposium on Biocomputing 10, 16-27 (2005). [PDF]
     
     Background Reading:
     ASMB: Chapters 11, 12 and 25
     
     
   • Efficient Computation of Small-Molecule Configurational Binding Entropy and Free Energy Changes by Ensemble Enumeration
     Presenting: Goke Ojewole.
     [Slides ppt] [Slides pdf]
     Primary Reading:
     
     Silver NW, King BM, Nalam MN, Cao H, Ali A, Kiran Kumar Reddy GS, Rana TM, Schiffer CA, Tidor B..
     Efficient Computation of Small-Molecule Configurational Binding Entropy and Free Energy Changes by Ensemble Enumeration. J Chem Theory Comput 9, 5098-5115 (2013). [PDF]
     
     
     Secondary Reading:
     
     Altman, M.D. Ali, A. Kiran Kumar Reddy, Nalam, M.N.S. Anjum, S.G. Cao H. Chellappan, S. Kairys, V. Fernandes, M.X. Gilson, M.K. Schiffer, C.A. Rana, T.M. Tidor, B.
     HIV-1 Protease Inhibitors from Inverse Design in the Substrate Envelope Exhibit Subnanomolar Binding to Drug-Resistant Variants. J Am Chem Soc 130, 6099-6113 (2008). [PDF]
     King BM, Silver NW, Tidor B. Efficient Calculation of Molecular Configurational Entropies Using an Information Theoretic Approximation. J Phys Chem 116, 2891-2904 (2012). PDF]
     
     
     Background Reading:
     ASMB: Chapters 26, 12, 24, and 25

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6. Monday Feb. 9, North 311
   
   
   
   Assignment:
   Do this quiz, and turn it in on Sakai by 1:00 PM, Feb. 9. Instructions. The quiz is based on the papers and discussion of Sparse Graphs in Protein Design.
   
   Project proposals were due on February 6th. See projects.
   
   We have two presenters today.
   • Conformational Dynamics of Single HIV-1 Envelope Trimers On the Surface of Native Virions
     Presenting: Amber Harold
     [Slides ppt] [Slides pdf]
     [Notes]
     Primary Reading:
     Munro JB, Gorman J, Ma X, Zhou Z, Arthos J, Burton DR, Koff WC, Courter JR, Smith AB 3rd, Kwong PD, Blanchard SC, Mothes W.
     Conformational dynamics of single HIV-1 envelope trimers on the surface of native virions. Science 346, 759-763 (2014). [PDF]
     
     Secondary Reading:
     econdary Reading:
     Pancera M, Zhou T, Druz A, Georgiev IS, Soto C, Gorman J, Huang J, Acharya P, Chuang GY, Ofek G, Stewart-Jones GB, Stuckey J, Bailer RT, Joyce MG, Louder MK, Tumba N, Yang Y, Zhang B, Cohen MS, Haynes BF, Mascola JR, Morris L, Munro JB, Blanchard SC, Mothes W, Connors M, Kwong PD.
     Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Nature 514, 455-461 (2014). [PDF]
     
     Background Reading:
     ASMB: Chapters 48, 47, 24
     
     
   • Design of Protein-Interaction Specificity Gives Selective bZIP-Binding Peptides
     Presenting: David Zhou.
     [Slides ppt] [Slides pdf]
     [Notes]
     Primary Reading:
     Grigoryan G, Reinke AW, Keating AE. Design of protein-interaction specificity gives selective bZIP-binding peptides. Nature 458, 859-864 (2009). [PDF]
     
     Secondary Reading:
     Apgar JR, Hahn S, Grigoryan G, Keating AE. Cluster expansion models for flexible-backbone protein energetics. J Comput Chem 30, 2402-2413 (2009). [PDF]
     
     Background Reading:
     ASMB: Chapters 9,10,11,12,25

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7. Date Monday Feb. 16, North 311
   
   We have two presenters today.
   • Fitting an Inter-Domain Orientation Distribution to RDC data
     Presenting: Yang Qi
     [Slides ppt] [Slides pdf]
     [Notes]
     Primary Reading:
     Kunze K, Shaeben H. The Bingham Distribution of Quaternions and Its Spherical Radon Transform in Texture Analysis. Mathematical Geology 36, 917-943 (2004). [PDF]
     Adjiman CS, Dallwig S, Floudas CA, Neumaier A. A Global Optimization Method, αBB, for General Twice-Differentiable Constrained NLPs - I. Theoretical Advances. Computers Chem. Engng 22, 1137-1158 (1998). [PDF]
     
     Background Reading:
     ASMB: Chapters 4-5, 15-17, 6, 7, 13.
     
     

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8. Date Monday Feb. 23, North 311
   
   We have two presenters today.
   • Pseudo-Contact Shifts
     Presenting: Francois Thelot.
     [Slides ppt]
     [Notes]
     Primary Reading:
     Otting G. Prospects for Lanthanides in Structural Biology by NMR. J Biomol NMR 42, 1-9 (2008). [PDF]
     Bertini I, Giachetti A, Luchinat C, Parigi G, Petoukhov MV, Pierattelli R, Ravera E, Svergun DI.
     Conformational Space of Flexible Biological Macromolecules from Average Data. JACS 132, 13553-13558 (2010). [PDF]
     Saio T, Yokochi M, Kumeta H, Inagaki F. PCS-based Structure Determination of Protein-Protein Complexes. J Biomol NMR 46, 271-280 (2010). [PDF]
     Kenwright B. A Beginners Guide to Dual-Quaternions. [PDF]
     Salamin E. Applicatoin of Quaternions to Computation with Rotations. Stanford AI Lab (1979). [PDF]
     Yagi H, Pilla KB, Maleckis A, Graham B, Huber T, Otting G. Three-Dimensional Protein Fold Determination from Backbone Amide Pseudocontact Shifts Generated by Lanthanide Tags at Multiple Sites. Structure 21, 883-390 (2013). [PDF]
     
     Background Reading:
     ASMB: Chapters 4-5, 15-18, 45, 6, 7, 33.
     
     
   • Principles for Designing Ideal Protein Structures
     Presenting: Alex Dao
     Primary Reading:
     [Slides ppt] [Slides pdf]
     [Notes]
     Koga N, Tatsumi-Koga R, Liu G, Xiao R, Acton TB, Montelione GT, Baker D. Principles for designing ideal protein structures. Nature 491, 222-227 (2012). [PDF]
     Background Reading:
     ASMB: Chapters 11-12, 45.
     

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9. Monday Mar. 2, North 311
   
   
   Please note the Assignment Due March 16.

   We have two presenters today.

   • Design of PDZ Domain Differentiable Peptides
     Presenting: Anna Lowegard.
     [Slides ppt]
     Primary Reading:
     Zheng F, Jewell H, Fitzpatrick J, Zhang J, Mierke DF, Grigoryan G. Computational design of selective peptides to discriminate between similar PDZ domains in an oncogenic pathway. J Mol Biol 427, 491-510 (2015). [PDF]
     Background Reading:
     ASMB: Chapters 9-12, 45.
     
     
   • Restricting HIV-1 Pathways for Escape Using Rationally Designed Anti-HIV-1 Antibodies
     Presenting: Lindsey Olivere
     [Slides ppt] [Slides pdf]
     [Notes]
     Primary Reading:
     Diskin R, Klein F, Horwitz JA, Halper-Stromberg A, Sather DN, Marcovecchio PM, Lee T, West AP Jr, Gao H, Seaman MS, Stamatatos L, Nussenzweig MC, Bjorkman PJ.
     Restricting HIV-1 pathways for escape using rationally designed anti-HIV-1 antibodies. JEM 210, 1235-1249 (2013). [PDF]
     

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10. Monday, March 9
    
    All Duke classes are cancelled today.

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11. Monday Mar. 16, North 311
    
    
    Assignment due on Sakai by 1:00 Today.
    Details: Submit a progress report for your project. 1-2 pages is enough, but you can write more if you want to discuss and get feedback. The report must begin with by the title of your project and a brief (2 sentence) summary of the project. It should clearly outline the approach you are taking, the problems you are trying to solve, what you have done so far, what you have accomplished so far, and how you plan to aproach the remaining tasks and challenges. Do not turn in a duplicate copy of your Feb. 6 proposal. Attempt to address any concerns/direction corrections raised by the instructors (us) when we read and (possibly) commented on your proposal.

    We have two presenters today.

    • Quantification of the Transferability of a Designed Protein Specificity Switch Reveals Extensive Epistasis in Molecular Recognition
      Presenting: Adi Mukund.
      [Slides ppt] [Slides pdf]
      [Notes]
      Primary Reading:
      Melero C, Ollikainen N, Harwood I, Karpiak J, Kortemme T. Quantification of the transferability of a designed protein specificity switch reveals extensive epistasis in molecular recognition. PNAS 111, 15426-15431 (2014). [PDF]
      
      
    • Reprogramming an ATP-Driven Protein Machine into a Light-Gated Nanocage
      Presenting: Chia-chieh Chu
      [Slides ppt] [Slides pdf]
      [Notes]
      Primary Reading:
      Hoersch D, Roh SH, Chiu W, Kortemme T. Reprogramming an ATP-driven protein machine into light-gated nanocage. Nat Nanotechnol 8, 928-932 (2013). [PDF]
      

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12. Monday Mar. 23, North 311
    
    We have two presenters today.
    • Background Reading:
      ASMB: Chapters 9-12, 45, 20.
    • Designed BH3 Peptides with High Affinity and Specificity for Targeting Mcl-1 in Cells
      Presenting: Ellie Zheng.
      [Slides ppt] [Slides pdf]
      [Notes]
      Primary Reading:
      Foight GW, Ryan JA, Gulla SV, Letai A, Keating AE. Designed BH3 peptides with high affinity and specificity for targeting Mcl-1 in cells. ACS Chem Biol 9, 1962-1968 (2014). [PDF]
      
      
    • Networks of bZIP Protein-Protein Interactions Diversified Over a Billion Years of Evolution
      Presenting: Jennifer Zou
      [Slides pdf]
      [Notes]
      Primary Reading:
      Reinke AW, Baek J, Ashenberg O, Keating AE. Networks of bZIP protein-protein interactions diversified over a billion years of evolution. Science 340, 730-734 (2013). [PDF]
      
      

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13. Monday Mar. 23, Nanaline Duke 437
    
    
    SBB Seminar
    
    • COMETS: Constrained Optimization of Multistate Energies by Tree Search
      Presenting: Mark Hallen

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14. Monday Mar. 30, North 311
    
    We have two presenters today.
    • Background Reading:
      ASMB: Chapters 42, 20-26, 30, 7, 39.
    • The Ensemble Nature of Allostery
      Presenting: Tahvi Frank.
      Primary Reading:
      Motlaugh HN, Wrabl JO, Li J, Hilser VJ. The ensemble nature of allostery. Nature 508, 331-339 (2014). [PDF]
      
      
    • Drift of HIV-1 Envelope Towards Resistance
      Presenting: Niklas Gahm
      [Slides ppt]
      Primary Reading:
      Bouvin-Pley M, Morgand M, Meyer L, Goujard C, Moreau A, Mouquet H, Nussenzwieg M, Pace C, Ho D, Bjorkman PJ, Baty D, Chames P, Pancera M, Kwong PD, Poignard P, Barin F, Braibant M.
      Drift of the HIV-1 envelope glycoprotein gp120 toward increased neutralization resistance over the douse of the epidemic: a comprehensive study using the most potent and broadly neutralizing monoclonal antibodies. J Virol 88, 13910-13917 (2014). [PDF]
      

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15. Monday Apr. 6, North 311
    
    We have two presenters today.
    • Background Reading:
      ASMB: Chapters 8, 17.5, 18.1.4, 15-18, 47-48.
    • Unusual Architecture of the p7 Channel from Hepatitis C Virus
      Presenting: Jin Liang.
      
      Primary Reading:
      OuYang B, Xie S, Berardi MJ, Zhao X, Dev J, Yu W, Sun B, Chou JJ. Unusual architecture of the p7 channel from the hepatitis C virus. Nature 498, 521-526 (2013). [PDF]
      
      Secondary reading:
      • Systematic solution to homo-oligomeric structures determined by NMR. Proteins 2015; 83(4):651--661.
      • A graphical method for analyzing distance restraints using residual dipolar couplings for structure determination of symmetric protein homo-oligomers. Protein Science 20(6):970-985 (2011) Mar 16. doi: 10.1002/pro.620. [Epub ahead of print] PMID: 21413097
        • [PDF]
      • Structure Determination of Symmetric Homo-oligomers by a Complete Search of Symmetry Configuration Space Using NMR Restraints and van der Waals Packing. Proteins 2006; 65(1):203-219.
        • [Medline, HTML, PDF, Supplementary materials, PDB Structure 2HYN]
      
      
    • A Universal Ebola Drug Target
      Presenting: Xuyan Ru
      Primary Reading:
      Clinton TR, Weinstock MT, Jacobsen MT, Szabo-Fresnais N, Pandya MJ, Whitby FG, Herbert AS, Prugar LI, Mckinnon R, Hill CP, Welch BD, Dye JM, Eckert DM, Kay MS. Design and characterization of ebolavirus GP prehairpin intermediate mimics as drug targets. Protein Science online, 1-18 (2014). [PDF]
      

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16. Monday Apr. 13, North 311
    
    Workshop
    
    In this class there will be no formal presentations but the course staff will answer questions to help you develop your course project. Please bring your questions about your project, and your progress on it and we will answer your questions in a group setting. Hooking up to the projector and talking in front of the overhead as you present your ideas and data will be encouraged. This will Facilitate the best questions and the best discussion.
    
    Obviously there will be a number of students attending the class so if you need private conversations please come to office hours.
    
    The entire class period today will be devoted to talking with each person who comes about their projects, looking at their data, results, and approaches, and giving advice on how to proceed. Other students in the class will also have the opportunity to chime in on their advice and comments in order to help everybody. This day is designed to help you get over any problems and hurdles and get you on the fast track to completing a really good project.
    
    

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17. Monday Apr. 20, North 311, 1:20 PM
    
    Please go to ACES, and fill out course evaluations! Thank you!
    Final Projects are Due Today.
    There is no Final Exam in this class.
    
    We have two presenters today.
    • A Deeply Knotted Protein Structure and How it Might Fold
      Presenting: Josh Welch
      Primary Reading:
      Taylor WR. A deeply knotted protein structure and how it might fold. Nature 406, 916-919 (2000). [PDF]
      
      
    • Background Reading:
      ASMB: Chapters 9-12, 25, 26.
    • Simultaneous prediction of binding free energy and specificity for PDZ domain-peptide interactions
      Presenting: Elise Bruguera
      Primary Reading:
      Crivelli JJ, Lemmon G, Kaufmann KW, Meiler J. Simultaneous prediction of binding free energy and specificity for PDZ domain-peptide interactions. J Comput Aided Mol Des 27, 1051-1065 (2013). [PDF]
      
    
    But wait! There is more! See below!

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18. Friday Apr. 24, Nanaline Duke 147 -- Note unusual time and place!
    
    
    Biochemistry Seminar: 12:00pm-1:00pm
    
    • Topic: Analysis and Design in Protein Binding and Enzyme Catalysis
      Presenting: Bruce Tidor, from MIT

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19. Friday May. 01, Nanaline Duke 147 -- Note unusual time and place!
    
    
    Biochemistry Seminar: 12:00pm-1:00pm
    
    • Measuring and modeling the binding specificity of structurally conserved protein interaction domains
      Presenting: Amy Keating, from MIT

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20. The class will be over, but here are some papers to remind you that it is good to continue to read papers, take notes, and discuss them! Enjoy your summer, it has been a fun class!
    Date: When you have time
    
    
    • Rational HIV immunogen design to target specific germline B cell receptors
      Presenting: TBD
      Primary Reading:
      Jardine, J. Julien, J.P. Menis, S. Ota, T. Kalyuzhniv, O. McGuire, A. Sok, D. Huang, P.S. MacPherson, S. Jones, M. Nieusma, T. Mathison, J. Baker, D. Ward, A.B. Burton, D.R. Stamatatos, L. Nemazee, D. Wilson, I.A. Schief, W.R.
      Rational HIV immunogen design to target specific germline B cell receptors. Science 10, 711-716 (2013). [PDF]
      

    • D-peptide inhibitors of HIV-1 entry
      Primary Reading:
      Welch BD, VanDemark AP, Heroux A, Hill CP, Kay MS. Potent D-peptide inhibitors of HIV-1 entry. PNAS 104, 16828-16833 (2007). [PDF]
      

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21. Final Quiz.
    What protein is pictured here?
    What do the blue and red dotted lines mean?
    How were they computed?
    Are they correct? Explain your answer.
    Date: Yes