Structural Bioinformatics

Transcription

1 Structural Bioinformatics Elucidation of the 3D structures of biomolecules. Analysis and comparison of biomolecular structures. Prediction of biomolecular recognition. Handles three-dimensional (3-D) structures.

2 Why bother with structures when we have sequences? In evolutionary related proteins structure is much better preserved than sequence. Structural motifs may predict similar biological function. Getting insight into protein folding. Recovering the limited (?) number of protein folds.

3 Applications Classification of protein databases by structure. Search of partial and disconnected structural patterns in large databases. Extracting Structure information is difficult, we want to extract new folds.

4 Applications (continued) Speed up of drug discovery. Detection of structural pharmacophores in an ensemble of drugs (similar substructures in drugs acting on a given receptor pharmacophore). Comparison and detection of drug receptor active sites (structurally similar receptor cavities could bind similar drugs).

5 A Life Sciences Data Integration Problem 3D Structure Pathways 26 March 2012 Introduction to Bioinformatics 5

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7 Wire-frame or ribbons display

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9 Protein Structural Comparison ApoAmicyanin - 1aaj Pseudoazurin - 1pmy

10 RCSB Protein Data Bank Agenda Introduction & Credits Basic Searching & Browsing Result Options Structure Summary Page Advanced Searching Tools & Education Summary Exercises consent 10 RCSB PDB:

11 Introduction & Credits Easy to navigate & customize consent 11 The RCSB PDB is RCSB managed PDB to by Access: 2 Molecule members of the of Month Experimental RCSB Data Structure Comparisons MyPDB Alerts Many Tools and Resources

12 PDB Statistics Homepage New Features News ` ` Latest Structures No use or reproduction consent 12 g

13 Structural Diversity - Constantly Increasing! Glucagon Insulin Many Enzymes Interferon Complexes Channels Molecular Machinery: A Tour of the Protein without express written Data Bank consent 13 rces/index.html

14 An Example of a Structure Summary Page Explore next Biological Assembly 2 asymmetric units β-strands α-helices loops consent 14 sugar-binding domains

15 More Background Information consent 15

16 Getting Started: Organization, Icons & Help Click to return to homepage Access from homepage Help Icons Help widget No use or reproduction consent 16

17 RCSB Protein Data Bank Agenda Introduction & Credits Basic Searching & Browsing Result Options Structure Summary Page Advanced Searching Tools & Education Summary Exercises consent 17 RCSB PDB:

18 Structure Deposition & Unique PDB Identifiers PDB ID examples: 2ara AraC transcription factor Customize 1lr5 Auxin Binding Protein 1e5s Proline hydroxylase Customize your g Deposit your structural data from the homepage Data will be validated and assigned a unique PDB ID homepage view consent 18 (not case-sensitive)

19 Basic Search Methods From the Search Homepage Search Help Booleans, wildcard & complex queries accepted g Many search methods in Top Bar Search consent 19

20 To more data A PDB ID Search Returns Structure Summary Page Structure title, ID, citations, descriptions, sources, methodology, structure & more Easy access to all search methods A Structure Summary page for every structure consent 20

21 Advanced Search & Latest Release Mouse over Show/Hide Left hand Search menu st of Results Click to see data distribution summary for this subset consent 21

22 Latest Release Search Left hand Search menu Click PDB ID, structure or title to go to Structure Summary Jump to a results page consent 22

23 New Structure Papers Search Left hand Search menu To related No structures use or reproduction & consent 23 articles To searchable PubMed abstract & NCBI PubMed abstract

24 Sequence Search Left hand Search menu Search methods Input PDB ID & chain ID or paste sequence consent 24 BLAST vs. FASTA: See RCSB PDB Help or OpenHelix tutorials

25 Chemical Components Search Left hand Search menu No use or reproduction consent 25

26 Unreleased Entries Search Left hand Search menu consent 26 Find the current status of a structure On hold, processing, withdrawn, & more

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33 RCSB Protein Data Bank Agenda Introduction & Credits Basic Searching & Browsing Result Options Structure Summary Page Advanced Searching Tools & Education Summary Exercises consent 33 RCSB PDB:

34 Structure Summary Page Enter 2arc 2arc Report tabs Title & ID One for every structure Organized similarly It provides access to a wealth of data Customizable with a widget framework Re-arranged sections in red Use Reset Layout to return to default Reset Layout consent 34 Menu s Primary Citation Molecular Description Source Ligand Component Related Entries Source Ligand Related Component Entries External Data (orange) Images & Viewing Options MyPDB Experimen Deposition t Summary Details Experimen MyPDB t Deposition Details Summary

35 Structure Summary Page - Top Reports Title, ID Citation AraC AND L-arabinose consent 35

36 Structure Summary Page - Top, Part 2 Looking at Structures Education section Asymmetric Unit options: Toggle through views Larger image consent 36 Click here

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39 Sequence Report Graphic of secondary structures Choose domain assignments or annotations from dropdown menu Specify how you want to view graphic et viewing preferences Results Tabs Select more annotations consent 39 References below

40 SCOP Annotations Report Database links CATH PFAM SBKB consent 40 Customize

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42 3D Similarity Report Scroll to Download & Help sections consent 42

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45 Methods Report Precise experimental details Organized similarly Mouse over to read definitions Sections depend on methodology consent 45

46 Links Report SCOP & CATH Scroll down to consent 46

47 RCSB Protein Data Bank Agenda Introduction & Credits Basic Searching & Browsing Result Options Structure Summary Page Advanced Searching Tools & Education Summary Exercises consent 47 RCSB PDB:

48 Advanced Search Access & Basics Query Types consent 48 Access from homepage top or left side search menu

49 Advanced Search - Number of Entities Query Protein 5 5 consent 49 Use Result Count to see how many results you will obtain Click on Add Search Criteria to add a query box

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51 Adding More Query Boxes Macromolecule Type Experimental Method Remove Similar & Match ALL or ANY Structur es vs. ligands, start over, or submit query consent 51

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53 RCSB Protein Data Bank Agenda Introduction & Credits Basic Searching & Browsing Result Options Structure Summary Page Advanced Searching Tools & Education Summary Exercises consent 53 RCSB PDB:

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59 An Information Portal Summary Many search options Special features to keep you current Lots of tools & services consent 59 Customize view

60 A Protein Information Goldmine Structure Summary pages provide detailed results Easy ways to visualize & manipulate structures No use or reproduction consent 60

61 RCSB Protein Data Bank Agenda Introduction & Credits Basic Searching & Browsing Result Options Structure Summary Page Advanced Searching Tools & Education Summary Exercises consent 61 RCSB PDB:

62 Sequence Mapping Linking to Domain data, efamily PDBechem ligand data Electron Density Visualisation AstexViewer PDBePro, PDBelite PISA biological assemblies Active sites Fold matching Surface Matching

63 Protein Databank in Europe (PDBe) group Is one of the four sites around the world that where 3D structures may be deposited. Provides stable and clean repository of macromolecular structure data. Has services that allow users to access, search and retrieve structural data from a single web access point.