1 / 25

What is Protein structure?

What is Protein structure?. Sang Hoon Kim. Post Reductionism. Data processing of biological Information Rightly interpretation of biological data So, bioinformatics is more important And We need new paradigm. Bioinformatics. DNA chip analysis Protein engineering or modeling

kalb
Download Presentation

What is Protein structure?

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. What is Protein structure? Sang Hoon Kim

  2. Post Reductionism • Data processing of biological Information • Rightly interpretation of biological data • So, bioinformatics is more important • And We need new paradigm

  3. Bioinformatics • DNA chip analysis • Protein engineering or modeling • Pattern analysis tool • Alignment tool and algorithm

  4. Importance of 3D structure

  5. Analysis of protein structure • Residue conformation • Periodic, non-periodic second structure • Residue burial and interactions • Association of secondary structure • Fold of protein domain • Evolution of protein

  6. Principle of protein structure • Primary structure (20 amino acids) • Secondary structure ( Alpha structure and beta structure ) • Tertiary structure ( motif, domain ) • Quaternary structure

  7. Definition of some words • Ramanchandran plot - A plot that show the ranges of bond angles that are permissible and the main type of structure of an L-polypeptide chain , (  = c-c = c-n) • Motif • Specific geometric arrangement ex) -- motif, Greek key motif • Domain • Topological region having specific characteristics

  8. Dominant effects in protein folding • Net protein stability • The hydrophobic effect • Atomic packing • Conformational entropy • Electro static effect • Disulfide bridges

  9. Approaches to prediction • Sequence analysis • Secondary structure prediction • Tertiary structure prediction • Modeling of protein structures • Verification

  10. Protein fold recognition Predicted Fold ? Algorithm of Protein modeling Alignment of Secondary structure Analysis of Fold family Multiple Sequence alignment Secondary structure prediction Alignment of Sequence to structure Experimental data Comparative modeling Protein sequence Data base searching Homologue In PDB Protein model

  11. Sequence analysis • Pam matrix • Global alignment of closely related protein • Blasum • Local alignment • Blast(basic local alignment search tool) • The list of high scoring words • Compare the word list to the database • Extend alignment in both directions

  12. Identification of sequenced motifs • Make use of internet site for identification of sequence motifs • The algorithm is a set membership matrix where rows correspond to the type of residue and columns to positions in the motif • Prosite (http :// expasy.pku.edu.cn/prosite) • ATP/GTP binding site motif = [AG]-X(4)-G-k-[ST]

  13. Prediction of secondary structure • Empirical statical method • Based on studies of the data base of protein of known primary and secondary structure (ex : Chou-Fasman, GOR, nearst neighbor, neural network) • Lim method • Based on knowledge about the physical and chemical basis of protein structure • Predictprotein • http://www.embl-heidelberg.de/predictprotein/predictprotein.html

  14. Comparative modelling • Many of the models were built using rule-based procedure encodes as computer programs (composer, SYBYL) • Using Composer one can get an approximate model and subsequently the interatomic interactions could be optimized using Modeller and energy minimization

  15. Molecular mechanics and dynamics • Two methods from the basis of molecular mechanics – energy minimization and molecular dymamics • Energy minimization • Search very localized region of conformational space, search around the initial conditions • Identify minima in energy funtion • Molecular dynamic • Homology modeling, conformational searching, sampling as required in free energy calculations

  16. Docking ligands to proteins Atomic resolution protein structure Database of small molecule structure Remove undesired waters, ions, atoms Eliminate very flexible molecules Calculate active site hot spots Calculate partial atomic charge Calculate molecular potential Calculate solvation energies Next ligand Calculate an orientation in the site Evaluate receptor-ligand complementary Graphically evaluate best scoring ligands

  17. Molecular Modeling and Biochemical Characterization Reveal the Mechani- sm of Hepatitis B Virus Polymerase Resistance to Lamivudine(3TC) and Emtricitabine(FTC) • Journal of virology, May 2001, p. 4771-4779

  18. Chemical structure of dCTP, 3TCTP, FTCTP, ADVDP, LBVTP, and PCVTP

  19. Alignment of HBV polymerase/HIV-1RT sequence

  20. HBV polymerase homology model

  21. The YMDD region of the modeled HBV polymerase with a docked dCTP substrate

  22. Binding of 3TCTP to wild-type and Met552Val mutant HBV polymerase

  23. Confliction with a docked ADVDP

More Related