introduction to structural bioinformatics

A glimpse into the course material

Topic 1

Course Information

Curricula materials: Structural Bioinformatics, 2nd editionEditors: Gu and BournePublisher: Wiley-BlackwellYear: 2009 ISBN-10: 0470181052

Course website: http://coitweb.uncc.edu/~drlivesa/BINF6202.html

Syllabus: http://coitweb.uncc.edu/~drlivesa/BINF6202/BINF6202_syllabus.pdf

Acknowledgement: Many of the slides used in this class were originally created by Dr. Jun-tao Guo. Thanks for sharing Jun-tao!

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

2I1C4TRA

RNA Protein-RNA

Protein Functions

Catalysis: Enzymes

Structural proteins: keratin, actin, tubulin…

Signalling proteins: insulin, growth hormone…

Immunity: antibodies

Transport proteins: ion transport, O2 transport…

…

>1MBN:_ MYOGLOBIN (154 AA) MVLSEGEWQLVLHVWAKVEADVAGHGQDILIRLFKSHPETLEKFDRFKHLKTEAEMKASEDLKKAGVTVLTALGAILKKKGHHEAELKPLAQSHATKHKIPIKYLEFISEAIIHVLHSRHPGNFGADAQGAMNKALELFRKDIAAKYKELGYQG

Proteinname Protein

sequence

Protein structure

Oxygen storage

Protein function

Protein and Protein Structure

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=yh9Cr5n21EE

“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”.

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".

Experimental Methods for Structure Determination

“Protein Structure and Function”, Petsko GA and Ringe D

X-ray crystallography

Nuclear magnetic resonance (NMR)Protein

purification

Protein Data Bank (PDB)

http://www.rcsb.org/pdb/

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

Laskowski, RA. Thornton, JM. Nature Review Genetics, 9:141-151

Timeline of Structural Determination of Some Key Bio-molecules

Molecular Machinery: A Tour of the Protein Data Bank

Structure Visualization

Pymol image Gallery: http://www.pymol.org

Protein Structure Classification

Hou et al. PNAS 2005 102:3651-3656

Class (C), Architecture (A), Topology (T) Homologous superfamily (H).

“Evolutionary relationship?”

MVLSEGEWQLVLHVWAKVEADVAGHGQDILIRLFKSHPETLEKFDRFKHLKTEAEMKASEDLKKAGVTVLTALGAILKKKGHHEAELKPLAQSHATKHKIPIKYLEFISEAIIHVLHSRHPGNFGADAQGAMNKALELFRKDIAAKYKELGYQG

Protein Structure Prediction and CASP

CASP: Critical Assessment of techniques for protein Structure Predictionhttp://predictioncenter.org/

**Modified image from Yang Zhang’s lab at University of Michigan

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

Pazos and Sternberg, PNAS, 2004, 101:14754-14759

Prediction of Protein Function From Structure

Number of new functions

Hypothetical SCOP domains

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

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.”

Dynamic Personalities of Proteins

nitrogen regulatory protein C

My lab = Biophysics + Bioinformatics

Protein Design Problems

Annu. Rev. Biochem. 2008, 77:363 & Nature, 2009, 462:182

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