Tutorials for protein data bank and swiss PDB viewer

1. Tutorialsforproteindatabankandswiss PDBviewer 2010/04/19 Prof. Jinn-Moon Yang Yen-Fu Chen and Kai-Cheng Hsu http://gemdock.life.nctu.edu.tw/dock/download/20100419_spv.ppt http://gemdock.life.nctu.edu.tw/dock/download/20100419_spv.pdf http://ppt.cc/cnqT (ppt) http://ppt.cc/WWxd (pdf)

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. 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

23. Install and execute swiss pdb viewer

24. Workspace Layer info Main window Viewer Control panel

25. Move & Rotate Center Zoom Rotate Translate

26. Open control panel control panel

27. Load PDB1

28. Load PDB2

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. Bond length 1 angstrom (A) or 1 × 10−10 meters ?A 1.52A

37. Bond length ?A

38. Bond length

39. Hydrogen bond length ?A

40. Hydrogen bonds of helix

41. Hydrogen bond of helix

42. Hydrogen bonds of helix Helix

43. Hydrogen bonds of sheet Sheet Residue 50~55 201~207 323~328

44. Number of helix ?From residue 46~146

45. Change color

46. Visualization of biological assembly-color by chain

47. Change color by chain-act on Ribbons

48. Show residue properties-Change color by Type

49. 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

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