multiscale structural visualization with ucsf chimera · visualization-based data analysis methods...

3/18/2005

Multiscale Structural Visualization with

UCSF Chimera

Depts. of Pharmaceutical Chemistry and Biopharmaceutical SciencesResource for Biocomputing, Visualization, and Informatics

University of California at San Francisco

Tom Ferrin

UCSF

3/18/2005

Outline

Today:

Chimera overview

Introductory demo

Bluetongue virus demo

Tomorrow - Tom Goddard “hands-on” exercise:

Chimera Volume Viewer extension

Copy of this presentation available at:

www.cgl.ucsf.edu/home/tef/talks/EMANworkshop.pdf

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Cell

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Determining the Structures of Proteins and Assemblies

Structural information from…source: measurement and modelsresolution: low or high resolution

Sali, Earnest, Glaeser, Baumeister. From words to literature in structural proteomics. Nature 422, 216-225, 2003.

Resource for Biocomputing,

Visualization, and Informatics

We are an NIH Biomedical Technology ResourceCenter, funded by the National Center for ResearchResources. We create innovative computational andvisualization-based data analysis methods andalgorithms, turn these into easy-to-use softwaretools which we distribute to the scientific community,and apply these tools for solving a wide range ofgenomic and molecular recognition problems within thecomplex sequence structure function triad.

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Sample application areas

Insight into molecular structure and function:

Protein engineering

Drug design

Biomaterials design

Annotation of protein function from sequence andstructure

Gene annotation, characterization, and interpretation:

Pharmacogenetics - understanding and prediction ofvariation in drug response due to genetic factors

Mouse gene knock-outs for modeling of human disease

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UCSF Chimera -

an Extensible Molecular Modeling System

Chimera is an extensible interactive 3-D modeling system designedto allow developers to quickly incorporate novel visualizationalgorithms and analysis tools

Chimera runs on laptops/desktops and takes maximum advantageof low-cost, state-of-the-art graphics chips

$500 today buys you 3-D interactive graphics capabilities that cost $20,000 five years ago

Chimera has extensive documentation for users and developers toenable effective scientific studies to be accomplished rapidly andwith a “low entry barrier”

UCSFChimera

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Documentation and Distribution

DocumentationExtensive User’s GuideBasic Programmer’s Guide

TrainingOn-line “Getting Started” tutorialPeriodic workshops

PlatformsWindows 98/2000/XPMac OS XLinux, SGI, HP Alpha

AvailabilityDownload from our Research Resource Center web site aftersimple “click to accept” license agreement

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Chimera’s Built-in Features

Molecular Graphics:interactively manipulate stick, ball-and-stick, CPK, ribbon representations, andmolecular surfaceshighly intuitive model translation,scaling, and rotationinteractive color editingability to save high resolution images forpresentation and publicationstereo viewing

Chemical Knowledge:determination of atom types in arbitrarymoleculesability to add hydrogen atomshigh-quality hydrogen bond identificationselection of atoms/bonds by element,atom type, functional group, and aminoacid categoryinteractive bond rotation, distance, andangle measurements

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Chimera’s Programmability/Extensibility

Chimera is designed to allow developers toquickly incorporate novel algorithms andanalysis tools

Extensions can control standard Chimerauser interface features (e.g. camera, help,menus, toolbar), as well as create their owncustom graphical user interfaces

Extensions are written in the Pythonprogramming language

– Python is easy to learn, even for noviceprogrammers

– Python is object-oriented and providesfeatures needed for development ofcomplex codes

– ~30 extensions written to date

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Learn more about Python

Python Web site:

www.python.org

Good book:

“Learning Python”

by Mark Lutz & David Ascher

Available from

www.oreilly.com/catalog/lpython2

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Sample Chimera Extension

Multalign ViewerSimultaneously displays multiple protein sequencealignments and corresponding structure superpositions,calculates and displays consensus sequence andconservation histogram, and highlights correspondingregions in both sequenceand structure space

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Sample Chimera Extension

Molecular Dynamics TrajectoriesAll built-in Chimera analysis and display capabilities alsowork with trajectories. Support is provided for a numberof common programs: AMBER, CHARMM, GROMOS,MMTK, NAMD, PDB, and X-PLOR.

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Sample Chimera Extension

Movie RecorderCapture image frames from

Chimera and assemblethese into a movie file

Formats supported:MPEG-1

MPEG-2

MPEG-4

Quicktime

(New feature in release 2104)

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Sample Chimera Extension

ViewDockRapid screening of promising drug candidates found withthe UCSF DOCK program

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Sample Chimera Extension

Volume ViewerAn extension for visualizing three-dimensional numericaldata sets

Electrostatic potential

(surfaces)

Electron density

(mesh)

Electrostatic potential

(solids)

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Sample Chimera Extension

Multiscale Modelinguseful for exploring modelsof large molecular complexescombines volumevisualization and atomicresolution capabilitiesexample systems includeviruses and chromosomesGroEL model: 14 copies ofthe monomeric GroELcrystal structure docked toa 10.3 Å electron microscopemap

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Chimera Demonstration #1

Introduction to molecular representation and basic use

Files used: 2gbp.pdb

Features illustrated:

Opening files

Selecting and displaying atoms, bonds, and surfaces

Manipulating models: rotate, translate, scale, clip

Display styles: wireframe, sticks, balls&sticks, CPK

Command line

Additional information: UCSF Chimera - A Visualization System for ExploratoryResearch and Analysis, J. Comp. Chem., 25(13):1605-1612, 2004.

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Chimera Demonstration #2

Bluetongue Virus CorePDB structure 2btv by DavidStuart’s lab (Nature 395: 470-478, 1998)

Full particle 700 Å diameter,3.5 Å resolution, 1000 crystalsand 3x106 atoms (no hydrogens)Multiscale extension makes 60copies of unit cell–Outer layer: 260 trimers of VP7 proteinin 5 symmetry classes–Inner layer: 60 dimers of VP3

Extension focuses onhierarchical structurerelationships and their selectionand display

Additional information: Software Extensions to UCSF Chimera for InteractiveVisualization of Large Molecular Assemblies, Structure, 13(3):473-482, 2005.

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Acknowledgements

Staff:Dr. Conrad Huang, Tom Goddard, Greg

Couch, Eric Pettersen, DanGreenblatt, Al Conde, Dr. ElaineMeng

Collaborators (partial list):Patricia Babbitt, UCSFWah Chiu and Steven Ludtke, BaylorJohn Sedat and David Agard, UCSFDavid Konerding and Steven Brenner,

UCB

Funding: NIH National Center for Research

Resources, grant P41-RR01081

Further information:www.cgl.ucsf.edu/chimera