Lecture 3.41 Structure Tools and Visualization † Gary Van Domselaar University of Alberta † Slides Adapted from Michel Dumontier, Blueprint Initiative

Lecture 3.42 Visualization & Communication Visualization tools allow us to see 3D structure data communicate features about 3-D structures to colleagues illustrate biological processes (catalytic/binding) educate laypersons about structural biology Go beyond Rasmol & communicate other structural features surface shape –show the surface, transparent over a backbone hydrophobicity / charge –show the binding surfaces or charge complementarity mutations –making a simple model (e.g. 1 amino acid change)

Lecture 3.43 In this lecture we introduce Rasmol and CHIME –Good introductory packages for biomolecule visualization Cn3D for Structure Annotation –Good all around viewer that uses OpenGL graphics –Good annotation engine for exchanging information about 3D structure Swiss PDB Viewer (Deep View) –Make molecular surfaces –Align multiple proteins –Apply scoring functions –Simple, fast modeling including site-directed mutagenesis –Complex modeling including loop rebuilding PyMOL –Python based, can be used for scripting

Lecture 3.44 Rasmol & CHIME Developed by Roger Sayle Open source, binaries available – Widely used, simple to use (menus) for simple operations Complex operations require command-line interface

Lecture 3.45 Rasmol Developed by Roger Sayle Open source, binaries available – Widely used, simple to use (menus) for simple operations Complex operations require command-line interface

Lecture 3.46 Getting Rasmol Structure Files Uses PDB files:

Lecture 3.47 Working With the PDB File “select cys115.cb” “select lys116”

Lecture 3.48 Hen egg-white lysozyme and tri-N-acetylchitotriose

Lecture 3.49 Rasmol Help Quick Reference Card: – Rasmol Manual – Tutorials: – Gallery: –

Lecture CHIME CHIME: “Chemical mIME” A free molecular viewer web browser plugin based on Rasmol Developed by MDL Information Systems Inc: – Improves on Rasmol: –More commands –Hypertext button-controlled scripting –Animations

Lecture CHIME What you need to run CHIME: –Netscape / Mozilla / Internet Explorer –Windows or Macintosh –A web page designed to use CHIME –A PDB file

Lecture CHIME and Protein Explorer Protein Explorer: A website that works with CHIME to help you visualize your structures

Lecture Cn3D Developed by the NCBI Open source, binaries available Fast OpenGL Graphics Annotation Engine –Lets you mark up a protein at the residue level Can fetch a structure over the Internet Can display protein “movies” –NMR ensembles –Protein folding trajectories

Lecture Getting Cn3D Structure Files Uses MMDB files Entrez ( tightly coupled with MMDB structure databasehttp:// Retrieve using –MMDB identifier –PDB identifer –Conserved Domain Database –BLAST search –PubMed query –Text search

Lecture Hen egg-white lysozyme and tri-N-acetylchitotriose

Lecture ASN.1 Structure File (ascii) MMDB-ID PDB ID History Publications Chemical Graph - Molecule Graph - taxonomy - residue sequence - inter residue bonds - heterogens - solvent - Inter-molecule bonds - Annotation - Camera Settings

Lecture Global Style Settings

Lecture Create New Annotation Disulfide Cysteines 1.Select Residues 2.Menu>Style>Annotate 3.Create New Annotation 4.Give Name and Edit Style

Lecture Edit Style Options

Lecture Selective Annotation of Cysteine Disulfide Bridges

Lecture Annotation Menu Turn On/Off – Show/Hide selected annotation Move Up/Down – Change priority Show – Show annotation and affected residues Edit – Edit an existing annotation Move – Move the annotation to selected residues Delete – Delete the Annotation

Lecture Shortcuts Rendering: SpaceFill Coloring: Rainbow Rendering: Ball and Stick Coloring: Hydrophobicity

Lecture Another Salient Feature Show/Hide>Select by distance

Lecture Imports Import sequences –BLAST alignments Import structures –Structural Superposition

Lecture BLAST Create alignments between sequences –In this case, an alignment between the structure sequence and the natural sequence reveals missing N and C termini residues and a loop region, not resolved in structure.

Lecture Conserved Domain Alignments

Lecture Folding Simulations

Lecture NMR Solution Structures

Lecture Finishing Your Work Save –Annotations –Camera Settings Export –PNG image

Lecture Other Cn3D Resources Online Help Application Help

Lecture Swiss PDV Viewer at a Glance PDB structure viewer with structure utilities Superimposition to compare proteins and their components such as active/binding sites Measure angles, distances between atoms Manual or automated (Swiss-Model) homology modeling including loop modeling Threading (Fold recognition) Mutations and Energy minimization Electron density map reading and model building (crystallography data) Interface to POV-Ray rendering software

Lecture Main Interface Tons of menu options reasonably well categorized Button bar for image manipulation (center, zoom, move, rotate) and some structure measurement and mutation tools Layers window to select from multiple layers

Lecture Control Panel Select –Individual Residues (one or more) –All Residues –Chains –Secondary Structure Show –Backbone –Side chains –Labels –Molecular surface (VDW) –Ribbon Cartoons (Helices/Strands) –Colors (specify backbone +/- sidechain, labels, etc)

Lecture Alignment and Ramachandran Plot Alignment Window shows alignment of sequences to one another (structural superposition, threading / homology modelling) Ramachandran plot showing Phi-Psi angles of selected residues. Can move individual residues to new Phi-Psi angles.

Lecture Molecular Surfaces

Lecture Electrostatic Potentials Useful for evaluating the effects of a potential mutation Analysis of binding site

Lecture SPDBV Home Page

Lecture

Lecture Persistence of Vision (POV) RAY Visualization Ray tracing occurs from the camera to the scene Specify –Camera location –Light sources –Objects –Surface textures –Atmospheric media (fog, haze, or fire)

Lecture POV RAY

Lecture PovRay Molecules... Armand Tepper ‘s Energy minimized Yeast Cu-metallothionein from an averaged NMR structure. 6 copper atoms are in the reddish metal texture and the sulfurs of the coordinating cysteines appear in yellow. This picture features the new smoother ribbon feature (quality 2) implemented in SPDBV3.6b2. The surface is at detail level 3. mandhttp://wwwchem.leidenuniv.nl/metprot/ar mand

Lecture 3.442

Lecture POV Ray scene generators Swiss PDB Viewer can save file as POV scene PDB to POV converters available –MolPov (windows) –PPOVIT (PERL)

Lecture PyMOL Set of structure tools built on top of Python Supports all Standard Features Extensible, Scriptable Native Ray Tracer Freely Available: –

Lecture PyMOL Set of structure tools built on top of Python Supports all Standard Features Extensible, Scriptable Native Ray Tracer Freely Available: –

Lecture PyMOL External GUI Command line interface Standard menu bar Some Handy Buttons

Lecture PyMOL External GUI VIEWING WINDOW Mouse Bindings Movie Controls Command Line Named Groups Panel

Lecture PyMOL Actions Menu (A) VIEWING WINDOW Mouse Bindings Movie Controls Command Line Named Groups Panel

Lecture PyMOL Show Menu (S) VIEWING WINDOW Mouse Bindings Movie Controls Command Line Named Groups Panel

Lecture PyMOL Hide Menu (S) VIEWING WINDOW Mouse Bindings Movie Controls Command Line Named Groups Panel

Lecture PyMOL Labels Menu (L) VIEWING WINDOW Mouse Bindings Movie Controls Command Line Named Groups Panel

Lecture PyMOL Color Menu (C) VIEWING WINDOW Mouse Bindings Movie Controls Command Line Named Groups Panel

Lecture Hen egg-white lysozyme and tri-N-acetylchitotriose

Lecture Conclusions Several of the more powerful structure tools with visualization and structure manipulation features are freely available –Rasmol, Cn3D, Swiss PDB Viewer, PyMOL Mark up your structures to convey important and useful information Ray Trace output scenes for best rendering and artistic flash