1. A glimpse into the course material Topic 1

2. Course Information Curricula materials: Structural Bioinformatics, 2nd edition Editors: Gu and Bourne Publisher: Wiley-Blackwell Year: 2009 ISBN-10: 0470181052 Course website: http://coitweb.uncc.edu/~drlivesa/BINF6202.html Syllabus: http://coitweb.uncc.edu/~drlivesa/BINF6202/BINF62 02_syllabus.pdf Acknowledgement: Many of the slides used in this class were originally created by Dr. Jun-tao Guo. Thanks for sharing Jun-tao!

3. Crick, F.H.C. (1958): On Protein Synthesis. Symp. Soc. Exp. Biol. XII, 139-163. Crick, F. (1970): Central Dogma of Molecular Biology. Nature 227, 561-563. The Central Dogma of Molecular Biology Protein-DNA 2I1C 4TRA RNA Protein-RNA

4. Protein Functions Catalysis : Enzymes Structural proteins : keratin, actin, tubulin… Signalling proteins : insulin, growth hormone… Immunity : antibodies Transport proteins : ion transport, O 2 transport… …

5. >1MBN:_ MYOGLOBIN (154 AA) MVLSEGEWQLVLHVWAKVEADVAGHGQDILIRLFKSHPETLEKFDRFKHL KTEAEMKASEDLKKAGVTVLTALGAILKKKGHHEAELKPLAQSHATKHKI PIKYLEFISEAIIHVLHSRHPGNFGADAQGAMNKALELFRKDIAAKYKEL GYQG Protein name Protein sequence Protein structure Oxygen storage Protein function Protein and Protein Structure

6. Molecular modeling with kindergarten supplies Linus Pauling won the Nobel Prize in Chemistry in 1954 "for his research into the nature of the chemical bond and its application to the elucidation of the structure of complex substances". Pauling summarized his work on the chemical bond in The Nature of the Chemical Bond, one of the most influential chemistry books ever published. See: http://www.youtube.com/watch?v=yh9Cr5n21EEhttp://www.youtube.com/watch?v=yh9Cr5n21EE

7. “As a result of Kendrew's and Perutz' contributions it is thus becoming possible to see the principles behind the construction of globular proteins. The goal has been reached after twenty-five years' labour, and initially with only modest results” -- Professor Hagg The 1962 Nobel Prize in Chemistry Goes to… Max Perutz and John Kendrew "for their studies of the structures of globular proteins”.

8. The 1962 Nobel Prize in Physiology or Medicine… The Nobel Prize in Physiology or Medicine 1962 was awarded jointly to Francis Harry Compton Crick, James Dewey Watson and Maurice Hugh Frederick Wilkins "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material".

9. Experimental Methods for Structure Determination “Protein Structure and Function”, Petsko GA and Ringe D X-ray crystallography Nuclear magnetic resonance (NMR) Protein purification

10. Protein Data Bank (PDB) http://www.rcsb.org/pdb/

11. Yearly Growth of Total Protein Structures Year The first reported structure is myoglobin PDB was set up in 1971 As of Jan. 5, 2010, there are 57,769 protein structures

12. Laskowski, RA. Thornton, JM. Nature Review Genetics, 9:141-151 Timeline of Structural Determination of Some Key Bio-molecules

13. Molecular Machinery: A Tour of the Protein Data Bank

14. Structure Visualization Pymol image Gallery: http://www.pymol.org

15. Protein Structure Classification Hou et al. PNAS 2005 102:3651-3656 Class (C), Architecture (A), Topology (T) Homologous superfamily (H). “Evolutionary relationship?”

16. MVLSEGEWQLVLHVWAKVEADVAGHG QDILIRLFKSHPETLEKFDRFKHL KTEAEMKASEDLKKAGVTVLTALGAI LKKKGHHEAELKPLAQSHATKHKI PIKYLEFISEAIIHVLHSRHPGNFGA DAQGAMNKALELFRKDIAAKYKEL GYQG Protein Structure Prediction and CASP CASP: Critical Assessment of techniques for protein Structure Prediction http://predictioncenter.org/ **Modified image from Yang Zhang’s lab at University of Michigan

17.  Disordered region prediction  Transmembrane segment prediction  Solvent accessibility prediction  Residue-residue contact prediction  Side-chain packing prediction  Secondary structure prediction  Loop modeling Sub-problems of Protein Structure Prediction **Images from Pondr and Rost, 1998

18. Pazos and Sternberg, PNAS, 2004, 101:14754-14759 Prediction of Protein Function From Structure Number of new functions Hypothetical SCOP domains

19. Prediction of Protein Function From Structure Watson et al. J Mol Biol. 2007 Apr 13;367(5):1511-22 Breakdown of prior information for the 282 MCSG structures

20. Dynamic Personalities of Proteins Richard Feynman said, “ Everything that the living things do can be understood in terms of the jigglings and wigglings of atoms. ”

21. Dynamic Personalities of Proteins nitrogen regulatory protein C

22. My lab = Biophysics + Bioinformatics

23. Protein Design Problems Annu. Rev. Biochem. 2008, 77:363 & Nature, 2009, 462:182

24. Protein-protein Docking and CAPRI **Image from San Diego Supercomputer Center at UC San Diego http://www.sdsc.edu/Gallery/vs_protein_docking.html CAPRI: Critical Assessment of PRediction of Interactions