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Tutorials for protein data bank and swiss PDB viewer

Tutorials for protein data bank and swiss PDB viewer. 2010/04/12 Prof. Jinn-Moon Yang Yen-Fu Chen and Kai-Cheng Hsu. http://140.113.239.67/spv.ppt. Contents. Introduction of protein structures Using thymidine kinase as an example Download and install Tutorial

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Tutorials for protein data bank and swiss PDB viewer

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  1. Tutorialsforproteindatabankandswiss PDBviewer 2010/04/12 Prof. Jinn-Moon Yang Yen-Fu Chen and Kai-Cheng Hsu http://140.113.239.67/spv.ppt

  2. Contents • Introduction of protein structures • Using thymidine kinase as an example • Download and install • Tutorial • Download protein structures from PDB • Basic Operation • Advance Operation • Resources for tutorial • http://www.youtube.com/watch?v=yFE3CAHNkZg&feature=related

  3. Introduction of protein structures • Proteins present in all biological organisms • Polymers of amino acids (20 L-α-amino acids) • Nanoparticles • Perform particular biochemical functions Transcription and translation Cell regulation and catalysis reactions stemcells.nih.go: Early Development Nature:  Mattson, M. Nature. 422, 385-387 (2003)

  4. Introduction of protein structures • To enable to perform protein’s biological function, protein fold into one or more specific spatial conformations driven by noncovalent interactions • Hydrogen bonding, ionic interactions, van der Waals forces and hydrophobic packing • 3D protein structures are necessary for understanding the functions of protein at molecular level Protein structure: from amino acid to quaternary structure Hemoglobin: oxy-deoxy states Adapted from Protein Structure in Wikipedia Adapted from structural biology Wikipedia

  5. Noncovalent interactions for protein structure and function • Ionic bond • A bond formed by the attraction between two oppositely charged ions • Hydrogen bond • An attractive interaction of a hydrogen atom with an electronegative atom, like N,O, and F Potential energy of Na and Cl Potential energy of Na and Cl

  6. Noncovalent interactions for protein structure and function • van der Waals force • Attractive or repulsive force between molecules • Hydrophobic interaction • The physical property of a molecule (known as a hydrophobe) that is repelled from a mass of water An example of hydrophobic interaction: Water drops on hydrophobic surface An example of van der Waals force: Gecko climbs on the glass

  7. Protein structure database:Protein data bank (PDB) • Techniques for determining atomic structures • X-ray crystallography, NMR spectroscopy and electron microscopy • PDB contains information about experimentally-determined structures of biological marcomoleculeas (proteins, and DNA/RNA) Proteins (1kim) X-ray NMR DNAs/RNAs (2k7e) EM http://www.pdb.org/ Biological complexes (1zrc)

  8. Search protein structures in PDB • PDB provides search by protein name, ligand, or structrue related keywords Search example: thymidine kinase (TK) • Function: DNA synthesis • Therapeutic: Anticancer and antivirus drug target

  9. Example: X-ray structures of virus’ thymidine kinase with substrates/inhibitors Protein name Source spices Experimental method has ligands

  10. Search result of “X-ray structures of virus’ thymidine kinase with substrates/inhibitors” 23 structures for these keywords PDB ID of this structure TK of virus TK with ligand (substrate) X-ray structure

  11. Structure and related data (1kim) Related data of this structure The title of this structure Visualization of biological assembly The citation of this structure

  12. Structure and ligand data (1kim) Ligand in this structure

  13. Structure and sequence data (1kim) Related data of this structure Sequence ID of 1kim in UniProtKB Structure classification ID of 1kim

  14. Advance inspection for protein structure: download structure from PDB • Save the data on your PC • Open the file on a structure viewer program (swiss PDBviewer, pymol, and etc.)

  15. Classification of Drug Development Protein (receptor) Structure High-Throughput Screening (HTS) Compound similarity search Unknown query Similar compounds SBDD or de novo design Structure-based Drug Design (SBDD) Known DDT 2002 Known Unknown Compound structure

  16. Discovering new leads HTS SBDD Yellow: virtual screening (SBDD) Blue: high-throughput screening (HTS) • There are more than 5 H-bond donors. • The molecular weight is over 500. • The LogP is over 5. • There are more than 10 H-bond acceptors. Curr. opin. Chem. Biol. 2002, 439

  17. Drugs derived from structure-based approaches Drug Discovery Today, 10, 895, 2005

  18. Drug Discovery Today, 10, 895, 2005

  19. TutorialforSwissPDBviewer

  20. Download and install • Download Swiss PdbViewer • http://spdbv.vital-it.ch/download.html • Download user guide • http://spdbv.vital-it.ch/Swiss-PdbViewerManualv3.7.pdf • Tutorial video (English) • http://www.youtube.com/watch?v=nYT5qwtfNew&feature=related • http://www.youtube.com/watch?v=yFE3CAHNkZg

  21. Downloadpage

  22. Install and execute swiss pdb viewer

  23. Workspace Layer info Main window Viewer Control panel

  24. General Terms Secondary Structure (Ribbon) Chain Residue Arginine Main chain Side chain Gray: C atom Blue: N atom Red: O atom Atom radius A protein may have multiple chains

  25. Load PDB1

  26. Load PDB2

  27. Move & Rotate Center Zoom Rotate Translate

  28. Open control panel control panel

  29. Display or hide residues-for some residues Press left button of mouse

  30. Display or hide residues-for all residues Press right button of mouse

  31. Display or hide side chains of residues

  32. Display or hide residue labels GLU111

  33. Display or hide atom radius

  34. Render in solid 3D

  35. Show secondary structures -Display or hide ribbons

  36. Change color

  37. Visualization of biological assembly-color by chain

  38. Change color by chain-act on Ribbons

  39. Show residue properties-Change color by Type

  40. Show structure flexibility Change color by B-factor A low B-factor meaning that the position of the atom has been determined with accuracy High B-factor Low B-factor

  41. Other color types default atom colors Root mean square between 2 molecules Secondary Structure Selected residues Relative accessibility

  42. Analyze protein-ligand interactions-Select ligands (or residues) Press left button of mouse to select the ligand (THM, thymidine) of 1kim

  43. Identify binding site-Show protein (ribbon) and ligand (stick)

  44. Select residues in the binding site-Neighbors of selected residues

  45. Center selected residues

  46. H-bonds of the binding site-Compute H-bonds

  47. H-bonds between protein and ligand-Show H-bonds of selection

  48. H-bonds between TK and THM-Show residues from selection

  49. Show residue label Press right button of mouse • Q125 recognize the thymine moiety • Activity was decreased by over 90% if Q125 mutated (Biochemistry, 2000. 39: p. 4105-4111)

  50. van der Waal forces-Stacking interactions M128 and Y172 sandwich the thymine moiety Stabilize the binding of substrate (JBC, 1999. 274: p. 31967-31973)

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