1. Online Counseling Resource YCMOU ELearning Drive… School of Architecture, Science and Technology Yashwantrao Chavan Maharashtra Open University, Nashik – 422222, India

2. SEP-SBI074-CP02-05 Introduction Programmes and Courses SEP –SBT074- CP02-U02

3. School of Science and Technology, Online Counseling Resource… Credits  Academic Inputs by Sonali Alkari Faculty YCMOU Nagpur Centre, Faculty LAD college P.G. D of Biotechnology Research officer Ankur Seeds Pvt Ltd sonalisa_alkari@yahoo.co.in Sonalisaal@rediffmail.com 3© 2007, YCMOU. All Rights Reserved.

4. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.4 How to Use This Resource  Counselor at each study center should use this presentation to deliver lecture of 40-60 minutes during Face-To-Face counseling.  Discussion about students difficulties or tutorial with assignments should follow the lecture for about 40-60 minutes.  Handouts (with 6 slides on each A4 size page) of this presentation should be provided to each student.  Each student should discuss on the discussion forum all the terms which could not be understood. This will improve his writing skills and enhance knowledge level about topics, which shall be immensely useful for end exam.  Appear several times, for all the Self-Tests, available for this course.  Student can use handouts for last minutes preparation just before end exam.

5. School of Science and Technology, Online Counseling Resource… © 2007, YCMOU. All Rights Reserved.5 Learning Objectives  After studying this module, you should be able to: Discuss importance of data visulization State factors affecting structure of molecules. Explain various visulization Tools: Rasmol, VMD, Swiss-PDB viwer, Cn3D

6. School of Science and Technology, Online Counseling Resource… Data visualization:1  In bioinformatics, the majority of data is in abstract form that needs visualization technologies to enhance user understanding.  This need is most pronounced in the areas of sequence visualization, user interface development, protein structure visualization, and as a complement to numerical analyses, especially statistical analysis.  In each application area, the rationale for using graphics instead of tables or strings of data is to shift the user’s mental processing from reading and mathematics, logical interpretation to faster pattern recognition. 6© 2007, YCMOU. All Rights Reserved.

7. School of Science and Technology, Online Counseling Resource… Data visualization:2  Data visualization technology provides the clue in graphical displays which enhance immediate understanding of the data being presented.  Visualization technologies can provide context and indications of relative importance.  Data visualization techniques are applications of bioinformatics, from methods of generating 3-D renderings of protein structures to creating maps of the physical location of genes on the chromosomes.  Structure visualization helps researchers to visualize protein structure data. 7© 2007, YCMOU. All Rights Reserved.

8. School of Science and Technology, Online Counseling Resource… Data visualization:3  One of the primary activities in proteomics R& D is determining and visualizing the 3D structure of proteins in order to find where drugs might modulate their activity.  Other activities include identifying all of the proteins produced by a given cell or tissue and determining how these protein interact.  Understanding the docking of two proteins is greatly facilitated by visualizing the two structures interacting in 3D space.  Visualizing a protein’s tertiary structure is valuable in comparing protein structure prediction. 8© 2007, YCMOU. All Rights Reserved.

9. School of Science and Technology, Online Counseling Resource… Factors Affecting Structure of Molecule:1  Molecular geometry or molecular structure is the three-dimensional arrangement of the atoms that constitute a molecule.  Molecular geometries can be specified in terms of bond lengths, bond angles and torsional angles.  distance and angles, confer conformational specificity to proteins.  More than 90% of H-bond "valences" are usually satisfied and geometries cluster closely around consensus distances and angles 9© 2007, YCMOU. All Rights Reserved.

10. School of Science and Technology, Online Counseling Resource… Factors Affecting Structure of Molecule:2 The rigid peptide dihedral angle, ω (involving the backbone atoms C α -C'-N-C α ). The bond between C1 and N is always close to 180 degrees. The dihedral angles φ (involving the backbone atoms C'-N-C α - C'). psi ψ (involving the backbone atoms N-C α -C'-N 10© 2007, YCMOU. All Rights Reserved.

11. School of Science and Technology, Online Counseling Resource… Factors Affecting Structure of Molecule:3 Global features of structure Quarternary structure global fold Æ machine metaphore, Mimicry Residues that participate in ligand binding location of SNPs or sites and context of mutations, PTM sites shape Æ clefts, pockets, protrusions interfaces structural similarity Æ homology conformational changes Æ molecular mechanism 11© 2007, YCMOU. All Rights Reserved.

12. School of Science and Technology, Online Counseling Resource… Factors Affecting Structure of Molecule:4 dihedral angles 12© 2007, YCMOU. All Rights Reserved.

13. School of Science and Technology, Online Counseling Resource… Factors affecting Ligand Binding  Tight and specific binding implies that all features of the ligand will be recognized by the protein Binding sites.  Factors affecting ligand binding are  Salt-bridges  Bond-lengths  Size Hydrogen bonds  Negative/positive charges  Hydrophilic/hydrophobic interactions  Distances from coordinates 13© 2007, YCMOU. All Rights Reserved.

14. School of Science and Technology, Online Counseling Resource… B-factors:1  B-factors are isotropic temperature factors, i.e. they model the relationship between observed and theoretical electron density of an atom atrest by applying a spherically symmetrical thermal distribution to the density until it best matches the experiment.  "Real" devitions from ideality are neither isotropic nor thermally distributed, they can correspond to discrete disorder, dynamic mobility and will be influenced experimental error of measuremen and refinement problems. 14© 2007, YCMOU. All Rights Reserved.

15. School of Science and Technology, Online Counseling Resource… Different forms of Structure:1 CPK Line Trace 15© 2007, YCMOU. All Rights Reserved.

16. School of Science and Technology, Online Counseling Resource… Different forms of Structure:2 Cartoon LR 16© 2007, YCMOU. All Rights Reserved.

17. School of Science and Technology, Online Counseling Resource… Why Structure Visualization  Proteins rely upon the shapes and properties of key functional areas of their three-dimensional structures to carry out biological functions.  The ability of protein to perform biological function depends on the formation of a three-dimensional structure (fold) that is stable in the normal environment of the protein.  We can predict secondary structure of a protein sequence whose structure and function are unknown.  Proteins in a family descend from a common ancestor and typically have similar three- dimensional structures, functions, and significant sequence similarity. 17© 2007, YCMOU. All Rights Reserved.

18. School of Science and Technology, Online Counseling Resource… Visulaization Tools  The vast majority of bioinformatics-specific tools shareware utilities developed with government funding, supplemented with a few dozen commercial offering.  Many tools are hardware or process-specific.  Visualization technologies, visualization tools leverage the pattern-recognition capabilities of the viewer's visual apparatus as opposed to logical, intellectual capabilities.  The selection of visualization tool should be a function of ease of use, power, speed, special features, cost, hardware requirements, documentation and support and overall functionality. 18© 2007, YCMOU. All Rights Reserved.

19. School of Science and Technology, Online Counseling Resource… Visulaization Tools Visualization ToolExample Nucleotide locationMap viwer Protein structureSwiss-PDB Viwer, Webmole, Rasmol, Protein explorer, Cn3d, VMD, Molmol, Midasplus, phymol, chime, chimera 19© 2007, YCMOU. All Rights Reserved.

20. School of Science and Technology, Online Counseling Resource… RasMol Viewer  RasMol is a molecular graphics program intended for the visualization of proteins, nucleic acids and small molecules.  The program is aimed at display, teaching and generation of publication quality images.  The program was developed at the University of Edinburgh's Biocomputing Research Unit and the Biomolecular Structure Department at Glaxo Research and Development.  RasMol reads in molecular co-ordinate files in a number of formats and interactively displays the molecule on the screen in a variety of colour schemes and representations.  Rasmol is with Small footprint, easy to install, sufficient functionality for most tasks widely distributed, powerful commandline interface, scripta 20© 2007, YCMOU. All Rights Reserved.

21. School of Science and Technology, Online Counseling Resource… RasMol Viewer  RasMol can read a prepared list of commands from a `script' file (or via interprocess communication) to allow a given image or viewpoint to be restored quickly.  RasMol can also create a script file containing the commands required to regenerate the current image, or create a dynamic session.  Finally the rendered image may be written out in a variety of formats including both raster and vector PostScript, GIF, PPM, BMP, PICT, Sun rasterfile or as a MolScript input script or Kinemage.  The best site displaying the functionality of RasMol is still the "original" RasMol Home Page by Eric Martz. 21© 2007, YCMOU. All Rights Reserved.

22. School of Science and Technology, Online Counseling Resource… Cn3D - 1  Cn3D is a helper application for your web browser that allows you to view 3-dimensional structures from NCBI's Entrez retrieval service.  Cn3D runs on Windows, Macintosh, and Unix. Cn3D simultaneously displays structure, sequence, and alignment, and now has powerful annotation and alignment editing features.  Cn3D can correct structure and sequence data to locate residues in a crystal structure that correspond to known disease mutations and can display structure-structure alignment. 22© 2007, YCMOU. All Rights Reserved.

23. School of Science and Technology, Online Counseling Resource… Cn3D - 2 23© 2007, YCMOU. All Rights Reserved.

24. School of Science and Technology, Online Counseling Resource… Features in Cn3D  Improved sequence alignment algorithms  Automatic VAST alignment import  Taxonomy viewer  Re-written in C++ to improve performance and extendibility  Improved OpenGL rendering speed  New user interface using wxWindows  Complete alignment editing system, along with algorithms for constructing new alignments  Extensive structure and alignment annotation features  Detailed style control  High-resolution image export  Built-in help system 24© 2007, YCMOU. All Rights Reserved.

25. School of Science and Technology, Online Counseling Resource… Swiss-PDB Viewer  DeepView - Swiss-PdbViewer is an application that provides a user friendly interface allowing to analyze several proteins at the same time.  The proteins can be superimposed in order to deduce structural alignments and compare their active sites or any other relevant parts.  Amino acid mutations, H-bonds, angles and distances between atoms are easy to obtain thanks to the intuitive graphic and menu interface.  DeepView - Swiss-PdbViewer has been developped by Nicolas Guex (GlaxoSmithKline).  Swiss-PdbViewer is linked to SWISS-MODEL, an automated homology modeling server developed within the Swiss Institute of Bioinformatics (SIB) at the Structural Bioinformatics Group. 25© 2007, YCMOU. All Rights Reserved.

26. School of Science and Technology, Online Counseling Resource… DeepView 26© 2007, YCMOU. All Rights Reserved.

27. School of Science and Technology, Online Counseling Resource… Swiss-PDB Viewer  Working with these two programs greatly reduces the amount of work necessary to generate models, as it is possible to thread a protein primary sequence onto a 3D template and get an immediate feedback of how well the threaded protein will be accepted by the reference structure before submitting a request to build missing loops and refine side chain packing.  Swiss-Pdb Viewer can also read electron density maps, and provides various tools to build into the density.  In addition, various modeling tools are integrated and command files for popular energy minimization packages can be generated. 27© 2007, YCMOU. All Rights Reserved.

28. School of Science and Technology, Online Counseling Resource… Visual Molecular Dynamics: VMD: 1  VMD is a molecular visualization program for displaying, animating, and analyzing large biomolecular systems using 3-D graphics and built-in scripting.  VMD supports computers running MacOS-X, Unix, or Windows, is distributed free of charge, and includes source code.  VMD includes built-in support for high-end quad- buffered stereoscopic rendering which can be used in projection theatres as well as desktop graphics workstations.  Sterescopic display aids significantly in the perception of three dimensional structures and has been a key feature in VMD since its first release. 28© 2007, YCMOU. All Rights Reserved.

29. School of Science and Technology, Online Counseling Resource… Visual Molecular Dynamics:VMD:2  VMD also provides support for inexpensive game- oriented stereo glasses, and even anaglyphic (Red/Blue) stereo.  In addition to Tcl and Python scripts, VMD implements "plugin" interfaces which provide a means for extending VMD at run-time without the necessity to recompile the program.  The two primary types of plugins for VMD are 'molfile' plugins for reading and writing data files containing atomic, graphics, and volumetric data, and scripting extensions which implement new commands and user interfaces for performing tasks such as structure building, simulation setup, etc. 29© 2007, YCMOU. All Rights Reserved.

30. School of Science and Technology, Online Counseling Resource… Visual Molecular Dynamics:VMD:3  This page contains plugins which can be downloaded and installed in your copy of VMD, as well as any pertinent documentation that goes along with the plugins.  Download VMD: VMD is a molecular visualization program for displaying, animating, and analyzing large biomolecular systems using 3-D graphics and built-in scripting. Visit the VMD website for complete information and documentation 30© 2007, YCMOU. All Rights Reserved.

31. School of Science and Technology, Online Counseling Resource… ModView 31© 2007, YCMOU. All Rights Reserved.

32. School of Science and Technology, Online Counseling Resource… VMD:4 32© 2007, YCMOU. All Rights Reserved.

33. School of Science and Technology, Online Counseling Resource… What You Learn…  You have learnt :  In bioinformatics, the majority of data is in abstract form that needs visualization technologies to enhance user understanding  Structure visualization helps researchers in understanding of the data, drug designing.  Map viwer is useful in visualization of 3 D structure of nucleotide where as Rasmol, VMD, Swiss-PDB viwer, Cn3D useful in protein structure visulization. 33© 2007, YCMOU. All Rights Reserved.

34. School of Science and Technology, Online Counseling Resource… Critical Thinking Questions 1.What structural visualization? 2.Why its structural visualization important? 3.What are the structure visualization tools? © 2007, YCMOU. All Rights Reserved.34

35. School of Science and Technology, Online Counseling Resource… Hints For Critical Thinking Question 1.methods of generating 3-D of protein structures to creating maps of the physical location of genes on the chromosomes. 2.understanding of the data,relationship between structure and function. 3.Map viwer, Rasmol, VMD, Swiss-PDB viwer, Cn3D © 2007, YCMOU. All Rights Reserved.35

36. School of Science and Technology, Online Counseling Resource… Study Tips:1  Book1 Title: Molecular Cell Biology Author: Harvey Lodish, David Baltimore Publisher: W. H. Freeman and Company  Book2 Title: Principles of Biochemistry Author: AlbertL Lehninger Publisher:CBS Publishers & Distributors 36© 2007, YCMOU. All Rights Reserved.

37. School of Science and Technology, Online Counseling Resource… Study Tips:2  Book3 Title: Biochemistry Author: Lubert stryer Publishers: Freeman International  Book4 Title: Biochemistry Author: Keshav Trehan Publishers: Wiley Eastern 37© 2007, YCMOU. All Rights Reserved.

38. School of Science and Technology, Online Counseling Resource… End of the Presentation Thank You ! 38© 2007, YCMOU. All Rights Reserved.