User:Wayne Decatur/UNH BCHEM833 Structural Proteomics Introductory Lecture Fall 2012

From Proteopedia

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Contents 1 A Common Starting Point 2 Key Resources 3 Discussed Items 4 Molecular Visualization and Viewers 5 Example Structures Used or Discussed in Class 6 Notes and References 7 Additional Resources that may be helpful on interesting 8 Introduction to Proteopedia 9 Under the Hood 10 Jmol 11 The Structure Data 12 Protein Data Bank 13 Proteopedia 14 Types of Proteopedia pages 15 Topic Pages 16 User Pages 17 PDB Entry Pages 18 FirstGlance in Jmol 19 Structural Biology for Non-structural Biologists 20 Proteopedia Page Authoring 21 Proteopedia Scene Authoring and Adding Green Scene Links to a Page 22 Time or need permitting 23 Resources 23.1 Macromolecular Visualization 23.2 Small Molecule Visualization and Model Kits 23.3 Topic Pages - Education 23.4 Authoring Scenes and Views in Proteopedia and beyond 23.5 Modeling

A Common Starting Point

• IProtein App review placing topic in a broader context to show relevance and introduce concepts to be covered today
• Table of Contents from the May Issue of Science to focus on two Perspectives that further place topic in context, showing broad relevance, the related fields evolving, and give us an example we can keep using and provide one of may paths for those interested to explore further if they wish. (No particular reason for these as examples, other than the block of papers caught my eye.) Specifically the two Perspectives of interest:
  • Evans P. Biochemistry. Resolving some old problems in protein crystallography. Science. 2012 May 25;336(6084):986-7. PubMed PMID: 22628641.^[1]
    • Perspective on:
      • Karplus PA, Diederichs K. Linking crystallographic model and data quality. Science. 2012 May 25;336(6084):1030-3. PubMed PMID: 22628654^[2]
      • Liu Q, Dahmane T, Zhang Z, Assur Z, Brasch J, Shapiro L, Mancia F, Hendrickson WA. Structures from anomalous diffraction of native biological macromolecules. Science. 2012 May 25;336(6084):1033-7. PubMed PMID: 22628655.^[3]
  • Kaya E, Doudna JA. Biochemistry. Guided tour to the heart of RISC. Science. 2012 May 25;336(6084):985-6. PubMed PMID: 22628640.^[4]
    • Perspective on: Schirle NT, MacRae IJ. The crystal structure of human Argonaute2. Science. 2012 May 25;336(6084):1037-40. Epub 2012 Apr 26. PubMed PMID: 22539551 paper on Crystal Structure of Human Argonaute2 in complex with guide RNA^[5], which features 4ei1.

Key Resources

• Proteopedia
• Protein Data Bank
• PDBsum
• Protein Structure Initiative:Biology program
• The International Structural Genomics Consortium
• ConSurf-DB (The ConSurf Database) and The ConSurf Server
• Syllabus for Eric Martz's 2-day workshop on Macromolecular Visualization
• The "Top 5" 3D Molecular Visualization Technologies for non-structural biologists
• POLYVIEW-3D - FAST ROUTE- makes you not need to learn a software package to make publication quality images. Just fill out forms.

Discussed Items

• Methods for Determining Atomic Structures, hosted at the PDB
  • X-ray crystallography
    • Fraction and number of structures
    • Resolution and hydrogens.
  • NMR Ensembles of Models
• Figure 1 illustrates strategies for solving structures of GPCRs, from TiBS article by Tate^[6].
• PDB poster and quick reference guide
• PDB file format in Proteopedia
• Article entitled Consortium solves its 1,000th protein structure^[7] - the international Structural Genomics Consortium celebrates its focus on expensive but exciting targets. (Covers some of controversy about such approaches and mentions US-based Protein Structure Initiative:Biology program).
  • 1,000 structures and more from the MCSG. 2011. BMC Struct Biol. Jan 10;11:2. ^[8] "We show that the MCSG has met the stated goals of the PSI and use online resources and readily available function prediction methods to provide functional annotations for more than 90% of the MCSG structures. The structure-to-function prediction method ProFunc provides likely functions for many of the MCSG structures that cannot be annotated by sequence-based methods."
  • The Proteome Folding Project: Proteome-scale prediction of structure and function. 2011. BMC Struct Biol. Jan 10;11:2. ^[9].
• Secondary structure displayed under the Contents link at the PDBsum or the Sequence tab at the PDB.
• Molecular Visualization and Viewers
• For analysis of buried surface areas in structural complexes:
  • I suggest PDBsum reports. See Interface analysis servers. Example: 3sn6 Prot-prot interface report or 1aoi Prot-prot interface report
  • Calculate in PyMol --> http://www.pymolwiki.org/index.php/Get_Area
• Compare your protein to others, see Acknowledgments therein for references^[10]. Also see the '3D similarity' tab for each structure in the PDB].
• Introduction to Evolutionary Conservation and How to see conserved regions. Enolase is used for viewing structural conservation and illustrating ligands.
• Caveats:
  
  • Asymmetric Unit unit vs. the biological assembly or biological unit.
    • Also, good information comes up with the PQS button in Firstglance in Jmol.
    • Also see Looking at Structures: Introduction to Biological Assemblies and the PDB Archive.
    • Example is bar-headed goose hemoglobin.
  • Considering Biological relevance, which can involve Crystal contacts
  • Gaps and disorder
    • see Missing Residues and Disorder on the Temperature value page
    • Also see Intrinsically Disordered Protein
• 10th Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction

Molecular Visualization and Viewers

(Generally, arranged in order of increasing complexity:)

• Proteopedia
• Firstglance in Jmol
• Jena3D Viewer
• Polyview-3D = fancy PyMol views and animations made super easy via a web server with forms.
• Jmol for download
• DeepView - Swiss-PdbViewer
• PyMol
• UCSF Chimera

Example Structures Used or Discussed in Class

• Crystal Structure of Human Argonaute2 in complex with guide RNA
• A human G protein-coupled receptor (GPCR), the beta-2 adrenergic receptor, in complex with a G protein featured on the Proteopedia page on G protein-coupled receptors (GPCRs). This structure was in the news recently because of the Nobel Prizes being awarded. The specific structure featured is 3sn6, as described in 2011 ^[11][12]. A Perspective on the structure is in the same issue^[13].
• The Nucleosome
• Bar-headed goose hemoglobin is used for discussing biological unit.
• Enolase is used for viewing structural conservation and illustrating ligands.
• Crystal Structure of a Catalytically Active Substrate-Bound Box C/D RNP From Sulfolobus Solfataricus
• The Ribosome

Notes and References

1. ↑ Evans P. Biochemistry. Resolving some old problems in protein crystallography. Science. 2012 May 25;336(6084):986-7. PMID:22628641 doi:10.1126/science.1222162
2. ↑ Karplus PA, Diederichs K. Linking crystallographic model and data quality. Science. 2012 May 25;336(6084):1030-3. PMID:22628654 doi:10.1126/science.1218231
3. ↑ Liu Q, Dahmane T, Zhang Z, Assur Z, Brasch J, Shapiro L, Mancia F, Hendrickson WA. Structures from anomalous diffraction of native biological macromolecules. Science. 2012 May 25;336(6084):1033-7. PMID:22628655 doi:10.1126/science.1218753
4. ↑ Kaya E, Doudna JA. Biochemistry. Guided tour to the heart of RISC. Science. 2012 May 25;336(6084):985-6. PMID:22628640 doi:10.1126/science.1223549
5. ↑ Schirle NT, Macrae IJ. The Crystal Structure of Human Argonaute2. Science. 2012 Apr 26. PMID:22539551 doi:10.1126/science.1221551
6. ↑ Tate CG. A crystal clear solution for determining G-protein-coupled receptor structures. Trends Biochem Sci. 2012 Sep;37(9):343-52. Epub 2012 Jul 10. PMID:22784935 doi:10.1016/j.tibs.2012.06.003
7. ↑ Ledford, H. Consortium solves its 1,000th protein structure. Published online 30 September 2010. Nature doi:10.1038/news.2010.500
8. ↑ Lee D, de Beer TA, Laskowski RA, Thornton JM, Orengo CA. 1,000 structures and more from the MCSG. BMC Struct Biol. 2011 Jan 10;11:2. PMID:21219649 doi:10.1186/1472-6807-11-2
9. ↑ Drew K, Winters P, Butterfoss GL, Berstis V, Uplinger K, Armstrong J, Riffle M, Schweighofer E, Bovermann B, Goodlett DR, Davis TN, Shasha D, Malmstrom L, Bonneau R. The Proteome Folding Project: proteome-scale prediction of structure and function. Genome Res. 2011 Nov;21(11):1981-94. Epub 2011 Aug 8. PMID:21824995 doi:10.1101/gr.121475.111
10. ↑ I don't see SCOP (Structural Clasification of Proteins) listed there but is listed in analysis towards top of the page.
11. ↑ Rasmussen SG, DeVree BT, Zou Y, Kruse AC, Chung KY, Kobilka TS, Thian FS, Chae PS, Pardon E, Calinski D, Mathiesen JM, Shah ST, Lyons JA, Caffrey M, Gellman SH, Steyaert J, Skiniotis G, Weis WI, Sunahara RK, Kobilka BK. Crystal structure of the beta2 adrenergic receptor-Gs protein complex. Nature. 2011 Jul 19;477(7366):549-55. doi: 10.1038/nature10361. PMID:21772288 doi:10.1038/nature10361
12. ↑ Chung KY, Rasmussen SG, Liu T, Li S, DeVree BT, Chae PS, Calinski D, Kobilka BK, Woods VL Jr, Sunahara RK. Conformational changes in the G protein Gs induced by the beta2 adrenergic receptor. Nature. 2011 Sep 28;477(7366):611-5. doi: 10.1038/nature10488. PMID:21956331 doi:10.1038/nature10488
13. ↑ Schwartz TW, Sakmar TP. Structural biology: snapshot of a signalling complex. Nature. 2011 Sep 28;477(7366):540-1. doi: 10.1038/477540a. PMID:21956322 doi:10.1038/477540a

Additional Resources that may be helpful on interesting

• Page from a 2011 Workshop given by Wayne Decatur that has a wealth of information for further exploring
• Orientations of Proteins in Membranes (OPM) database from the University of Michigan (Ann Arbor, Michigan, USA), and knowing the spatial arrangement of protein with respect to the hydrocarbon core of the lipid bilayer and other details of topology
• POLYVIEW-3D makes publication-quality images and animations of structures via a form you fill out
• Eric Martz's future page for a class an introductory class he is teaching in 2013
• Students at UMASS in classes associated with Chemistry-Biology Interface program design presentations for showing on the Molecular Playground. An example is Relenza for the Molecular Playground.
• Molecular modeling and visualization software

Introduction to Proteopedia

• Main Page
• Sightseeing by way of example "Case Studies" / "User Narratives"
  • Topics
    • main page--->Ribosome structure, spin, hover, measure distances, toggles, list, contributors --->page particular section ---> another page green links
    • via search---> The Glutamate Receptor (GluA2) quality, popup, section window
  • Open-ended Gateway
    • learn of a structure in a meeting (Robert Milllar talk on Saturday) ---> Pubmed search result---> 2rh1
      • Sites
      • ConSurf
      • Firstglance in Jmol
    • new publication ---> 3rze Sites
      • note where link to 3D structure at Nature publication goes
  • Student aid - Proteopedia:Table of Contents -->Metabolism -->Carbohydrate Metabolism -->Citric Acid Cycle--> Citrate Synthase morphs and reaction steps in second section
  • Lecturing
    • User:Eric Martz/Nucleosomes
    • resources for this workshop as listed under Workshops and Seminars on my user page as Workshop for the NASCE Meeting at the University of Michigan, Ann Arbor, MI July 13 2011
  • Structural Biology Resource
    • X-ray crystallography ---> Quality assessment for molecular models
    • Cation-pi interactions
  • Student Projects
    • Students at UMASS in classes associated with Chemistry-Biology Interface program design presentations for showing on the Molecular Playground
  • Journal Club --> RecG Bound to Three-Way DNA Junction
  • Communicating specific ideas in context of structure --> e-mail a link to a Sandbox, e.g. Sandbox CsrA
  • Group meeting ---> Proteopedia:Workbench, also good for preparing for publication
  • Publications
    • Collaboration with BAMBEd --->Category:Featured_in_BAMBED ----> Ramachandran Plot
    • Interactive 3D Complements

Under the Hood

• Wiki implementation, very specialized
  • references
    • Create a page for example with references
  • other technical aspects related to Jmol and other media
• Jmol

Jmol

• Jmol
  • The Application
  • The Java Applet - Demonstration with Human Follicle-Stimulating Hormone Complexed with its Receptor
• Advanced Options
  • Console
  • Compare Command Demonstration
  • Sculpting - Simple example of that here
  • 3D options - Demo with Hormone

The Structure Data

• everything centers around an Atomic coordinate file
• Experimental vs theoretical sources

Protein Data Bank

• nearly 75,000 X-ray crystallography, NMR, and cryo-EM structures
• PDB statistics
• about 85% are crystallographic structures - hydrogens anyone? Hydrogen in macromolecular models
• Isomesh of electron density helps illustrate how crystallographic models get built using a portion of one
• Caveat: Keep in mind these are models - Not all models created equally
  • one gauge Resolution noted with a link on each PDB entry page

Proteopedia

• Proteopedia - interactive 3D encylopedia of macromolecular structures and structural biology resources to which scientists contribute and use to share structural biology content
• Help:Getting Started in Proteopedia
• User or Sandbox login
• We encourage you all to become users of any sort. If you become a registered, you can save information in your userspace regardless of your overall contribution to public spaces.

Types of Proteopedia pages

• Topic Pages
  • Macromolecular Structures
  • About Macromolecular Structure
• PDB Entry Pages
• User space Pages
• Sandbox Pages , see Help:Sandboxes
• Workbench Pages ,see Proteopedia:Workbench and Group:SMART:Workbench_SMART_Teams#
• Interactive 3D Complements (I3DC) - Journal of Biological Inorganic Chemistry
• Administrative
  • How To/Guides
  • Organizational/Table of Contents
  • Main Page - the main gateway

Topic Pages

• Additional examples of topic pages concerning structures
  • Hemolysin
    • Proteopedia pages can be exported for offline viewing using the toolbox on the left.
• Information and Resource Collection, as well
  • About Macromolecular Structure
  • Searching

User Pages

• Other users cannot edit pages in this space

PDB Entry Pages

• Proteopedia has an entry for every PDB entry (nearly 75,000) with interactive scene links and links to useful resources
  • Example 1p3v (PDB 4 digit alphanumeric accession number)
    • Evolutionary conservation - conserved patches are good candidates for functional sites: see explanation and caveat, and see also The ConSurf Database and The ConSurf Server Other examples: 4enl or 5cyt
      • Show how to use ConSurf Server - Be sure to choose to "Let me select the sequences for the analysis manually out of Blast results"

FirstGlance in Jmol

• Views and Convenience buttons
  • How many chains? - Use 3pla
  • Key Resources:
    • Biological Unit
    • Missing pieces?; PDBsum link on Proteopedia entry pages helpful for this as well
• Under adoptions on main page , there is Orientations of Proteins in Membranes (OPM) database from the University of Michigan (Ann Arbor, Michigan, USA), and knowing the spatial arrangement of protein with respect to the hydrocarbon core of the lipid bilayer and other details of topology could be useful for understanding the function of several proteins involved in endocrinology, example 2rh1
  • Also accessible via Membrane proteins from within Proteopedia

Structural Biology for Non-structural Biologists

• MolviZ "Top 5" by Eric Martz
• Polyview-3D = fancy PyMol views and animations made super easy via a web server with forms.
  • Example for 2rh1
    • Use overall structure with ligands off; under chain and color rendering chain a as cartoon and hide remaining; under individual residue highlight enter a:408:cf,a:290:ms from converter
    • 2rh1 from Polyview-3D (probably the gap in the cartoon is an artifact due to the way the numbering is for 2rh1 due to the chimeric nature of the receptor with lysozyme (see PDBSum
  • Makes animations too and/or morphs as well using a file with multiple models

Proteopedia Page Authoring

• Model of a wiki
• Sandbox - there is a "student" login that can be used by groups for editing these for teaching purposes
• Conveniences
  • Buttons for 3D structure windows and other commonly used items
  • Since a large amount of references are from PubMed, PMID all that is needed for references in text, combined with a reference list at end
• Proteopedia:How to Make a Page
• How to edit pages in Proteopedia
• Special:Upload List of allowed file types: png, jpg, jpeg, tiff, tif, gif, mgif, pdb, cif, mmcif, cml, mol, xyz, kin, mmol
• To do:
  • Try making a sandbox page
  • Add a subject or title to your page
  • Insert a 3D structure window on your page

Proteopedia Scene Authoring and Adding Green Scene Links to a Page

• Proteopedia's Scene Authoring Tools
• To do:
  • Load a structure 3ciy or previous scene
  • Set your scene. Undo/Redo features.
• Save your scene
  • Try it out and then add and improve. Repeat until you are happy with result.
• Add the scene to the page you made by pasting the text from the scene text box into the page editing box.
  • Return to scene authoring tools to make more scenes or improve the one you have.
  • If you update a scene, change the text on the page to designate playing of the new scene.

Time or need permitting

• Advanced scenes/toggles - Human Follicle-Stimulating Hormone Complexed with its Receptor has several examples
• Morphing allows displaying the visual transition between two molecular conformations.
• Pymol to Jmol conversion built into Proteopedia's Scene Authoring Tools
• Jmol works with small molecules too
  • • Works with small molecules too and even can do energy minimization with them
    • Can be used to show chemical reactions
• Recalling the Caveat: Keep in mind these are models -Not only are not all models models created equally, not even all portions of models are created equally

• Assessing structure
  • Resolution noted with a link on each PDB entry page
  • Temperature factors, also see demonstration here
  • Gaps, i.e. missing pieces (see above)
• Can't find an empirical 3D model for your sequence?
  • Use the sequence of your protein to search the Structural Genomics Target Database for crystal structures nearing publication.
  • Endeavor to generate a theoretical model by one of various means

Resources

Macromolecular Visualization

• Eric Martz's recent workshop at his list of workshops.
• Proteopedia - a scientific 'wiki' bridging the rift between 3D structure and function of biomacromolecules, Eran Hodis, Jaime Prilusky, Eric Martz, Israel Silman, John Moult and Joel L Sussman. Genome Biology 9:R121, August 2008 or doi:10.1186/gb-2008-9-8-r121
• About Macromolecular Structure
• FirstGlance in Jmol is very useful for exploring PDB entries or upload structure files.
• Jmol Protein Explorer's powerful Quickviews approach really helps quickly generate useful views. This effort is building Chime-based Protein Explorer to work with Jmol, and a few features may still not yet work.
• MolviZ "Top 5"
• MolviZ.Org
• Protein Explorer's Glossary
• Jmol Application
• PyMol
• Polyview-3D, fancy PyMol views and animations made super easy via a web server with forms.
• eMovie,a PyMol plug-in for macromolecular movie-making.

Small Molecule Visualization and Model Kits

• CheMagic Virtual Molecular Model Kit
• The Jmol Interface by Mike Evans at University of Illinois has a model kit interface and easy ways to arrows and items.
• ChemCanvas, an open source chemical diagram editor
• ChemTube3D has interactive animations and structures of molecules and reactions important in chemistry.
• Service allowing young people to look up a molecule and blow it up and put it back together
• ChemDoodleWeb Integrated with Jmol
• Scribmol is a ChemDoodleWeb Integrated with Jmol application found at a utilities page (french) with other useful visualization tools.
• CheS-Mapper (Chemical Space Mapper) is a 3D-viewer for chemical datasets with small compounds. It on the fly divides large datasets into clusters of similar compounds, arranging them in 3D space, such that their spatial proximity reflects their similarity. It is an open-source Java application, based on the Java libraries Jmol, CDK, WEKA, and utilizes OpenBabel and R.

Topic Pages - Education

• Teaching Strategies Using Proteopedia
• Teaching Scenes, Tutorials, and Educators' Pages

Authoring Scenes and Views in Proteopedia and beyond

• Proteopedia:Video Guide
• Help:Getting Started in Proteopedia
• Proteopedia:How to Make a Page
• How to edit pages in Proteopedia ? Example 1, example 2, and example 3 of edited topic pages.
• Special:Upload List of allowed file types: png, jpg, jpeg, tiff, tif, gif, mgif, pdb, cif, mmcif, cml, mol, xyz, kin, mmol
• Proteopedia's Scene Authoring Tools
• Perform basic editing and creation of scenes in your Sandboxes
• Copying FirstGlance Scenes into Proteopedia
• User:Tom Gluick/glutamine synthetase (University of Maryland, Baltimore County). Includes instructions for using Jmol commands in the Jmol console for advanced scene authoring.
• Jmol Command Reference Manual for advanced scene authoring in Jmol using commands because direct scripting works for Proteopedia too.
• Comparison of Jmol tutorial-authoring systems
• Copying FirstGlance in Jmol Scenes into Proteopedia
• Jmol Protein Explorer's powerful Quickviews approach really helps quickly generate particular scenes or ideas for scenes to generate elsewhere. Using the information detailed here or at the JTAT site on extracting state scripts, it is possible to go from these views to Proteopedia scenes; however, as the version of Jmol differs there may be discrepancies and issues.
• Jmol Tutorial-Authoring Template (JTAT) describes and works for developing and viewing scenes offline or developing and viewing privately.
• Jmol Command Reference Manual for advanced scene authoring.
• Jmol Wiki
• Morphing allows displaying the visual transition between two molecular conformations.
• Polyview-3D, fancy PyMol views and animations made super easy via a web server with forms.

Modeling

• See the end of Eric Martz's recent workshop syllabus where he covers homology (more accurately, comparative) modeling.
• A Feb. 1st 2011 news item about Yang Zhang and his work.
• Mutating an amino acid in a protein - here with PyMOL and here with Swiss PDB-Viewer
• Homology modeling
  • Eric Martz's page on Homology Modeling
  • Swiss Model
  • Homology Models Database
  • Modbase -Database of Comparative Protein Structure Models
• Comparative Modeling
  • Zhang Server (I-TASSER)
• Ab Initio and Molecular Dynamics
  • Quark server
  • VMD - Visual Molecular Dynamics
• RNA modeling
  • Secondary Structure
    • The methods page for CompaRNA lists and provides links to several software and server-based programs for secondary structure prediction.
    • NASP is a parallel program for identifying evolutionarily conserved nucleic acid secondary structures from nucleotide sequence alignments. See the companion article.
  • 3D Structure
    • ModeRNA server is an online tool for RNA 3D structure modeling by the comparative approach, based on a template RNA structure and a user-defined target-template sequence alignment. Related to this is ModeRNA ModeRNA, which is a program for comparative modeling of RNA 3D structures. It requires a pairwise sequence alignment and a structural template to generate a 3D structural model of the target RNA sequence and allows for nucleotide modifications. See the companion article for the server.
• RNA-protein modeling
  • The software page at the Bujnicki Laboratory website hosts software for determining two medium-resolution, knowledge-based potentials for scoring protein-RNA models obtained by docking. See the companion article.