Before modern desktop computers because available, crystallographers built 3D structural models by hand –The earliest models such as that of myoglobin (Kendrew et al., 1958), were built from masses of rods, wires and spheres, so complex that molecule was lost in the web of the supporting metal framework As with many other areas of science, macromolecular structure determination took off with the advent of electronic computing and graphics technologies and thus macromolecular visualisation. The earliest attempts at electron representations of macromolecular model used a computer controlled oscilloscope to display the rotating image of a protein structure (Levinthal et al., 1968). One of the earliest and most widely used programs for constructing and manipulation molecular structures was FRODO (Jones, 1978). FRODO provided high-quality, interactive, colour images of electron density maps and structures. Gave the use the ability to fit a model into displayed density by moving fragments of the model or even invidual atoms. 1980s-1990s: visualization becomes cheaper with the start of Silicon Graphics and their graphics workstations -- owning an SGI workstation is still not cheap or routine FRODO remained in widespread use throughout the 1980s before eventually being superceded by O (Jones et al., 1991). RasMol developed by Roger Sayles as part of his graduate work in the early 1990s. Late 1990s-present: high quality graphics available on desktop PCs; software developers play catch- up Protein visualization - History

Visualization Objectives Structure –Backbone; secondary, tertiary & quaternary Side chain groups –Hydrophobic, charged, polar, acidic/base, etc. Cross-links –Hydrogen bonds, disulfide bonds Surfaces –VanderWaals, solvent-accessible Charge distributions, distances & angles, etc.

Common visualization styles To visualise a whole molecule for the purpose of showing its shape, a solid surface can be used C, N, S, HHelix Loop Sheet RainbowRainbow

Common visualization styles C, N, S, HHelix Loop Sheet RainbowRainbow Jane Richardson pioneered a style of prepresenting alpha helices as simple cylinders or broad, spiral ribbons, and beta-starnds as broas, flat ribbons (Richardson, 1985). This remains one of the most enduring and appealing ways of representing protein secondary structure.

Common visualization styles To visualize a whole molecule for the purpose of showing the position of each atom, a wireframe diagram can be used C, N, S, HHelix Loop Sheet RainbowRainbow

Visualisation strategies To focus attention on particular amino acids or atoms: display the protein backbone as a ribbon or cartoon, then select the atoms of interest and color them to contrast, or display them as sticks or spheres To show features of a protein surface (location of charges, etc) display the protein as a solid with the desired surface facing forward; color the surface by electrostatic potential or atom type To choose a good view for presentation, display the molecule in a non- display-intensive format (like ribbons or sticks) choose an orientation, and then add the more graphics- intensive elements such as surfaces and cartoons Good views for presentation clearly show the relationship of the feature you’re emphasizing to the structure as a whole, and are as uncluttered as possible while still showing detail of the feature

Software types Crystallographic model building: program allows interactive manipulation of structure model to fit to electron density Structure query: program provides clickable distance monitors, contact maps, Ramachandran maps, and other information about the molecule in addition to an interactive visualization Presentation: program provides high-resolution color or black and white graphics with or without an interactive visualization

Visualisation styles and software RasMol: Structure interrogation, ppresentation. Lightweight but very powerful interactive structure viewer. The Swiss-Army knife of macromolecular visualisation. PyMOL: Powerful python-based visualisation program. Input is via both a graphical user interface and a python-based command language. VMD: Structure analysis and presentation, with an emphasis on molecular dynamics. Includes numerous tools for dealing with molecular dynamics, trajectories and models.General-purpose interactive visualisation. Chimera: Basic model building, model query, presentation. A modular package for all aspects of molecular visualisation, from simple model building through production of high-quality images Swiss PDB viewer: Structure interrogation, ppresentation and bbasic modelling. Swiss- PdbViewer is an application that provides a user friendly interface allowing to analyse several proteins at the same time. Xfit: Electron density map interpretation, mmodel building and presentation. Part of XtalView crystallography package. Sports a comprehensive set of model building tools, most notably the ability to generate electron density from structure factors on the fly. O: Electron density map interpretation and mmodel bbuilding. Extremely powerful, if somewhat unintuitive, model-building package. One of the most widely used model-building packages, certainly in academia.

Tutorials Pymol Swiss Prot VMD (Michelle) Early next week