Transcript hanson_echeminfo_10_14_2009

Jmol and its Potential for Data Mining
and Molecular Visualization
in Drug Discovery
Robert M. Hanson
Department of Chemistry, St. Olaf College
Northfield, MN 55057
Echeminfo – Applications of Cheminformatics
and Chemical Modelling to Drug Discovery
Bryn Mar, Pennsylvania
Oct. 14, 2009
The Jmol Molecular Visualization Project
• Open-source
• Jmol.sourceforge.net
• Active user/developer community
about 400 “users”
about 150 “developers”
collectively 23,000 list messages
The Jmol Community
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Professional graphics designers
Professional developers
Bioinformatics/Cheminformatics Professionals
Professors, graduate students, undergraduates
• Generally one of three focal points:
– Research
– Publishing
– Education
The Jmol Community
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Professional graphics designers
Professional developers
Bioinformatics/Cheminformatics Professionals
Professors, graduate students, undergraduates
• Common Goals:
– Communication
– Web-based delivery
Jmol History
• Jmol version 9 (2004)
– Chime replacement
– Small molecules
– Minimal functionality
Jmol History
• Jmol version 10 (2005)
– better graphics
– Chime/RasMol
replacement
– more functionality
Jmol History
• Jmol version 11.0 (2007)
– surfaces
– crystallographic symmetry
Jmol History
• Jmol version 11.2 (2007)
• Jmol version 11.4 (2008)
• Jmol version 11.6 (2008)
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better perspective model
“navigation” mode
better graphics
export to POV-Ray, VRML
signed applet
extensive scripting
Jmol History
• Jmol version 11.8 (2009)
• Jmol version 11.9 (2009)
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data-mining mode
quaternion-based analysis
“live” images
Jmol consolidated file format
Jmol Innovations: Surfaces
• As the current principal developer and project manager
of the Jmol molecular visualization project, I get requests
periodically for new visualization ideas.
Jmol Innovations: Surfaces
load 3dfr.pdb;isosurface select(protein) ignore (not
solvent and not protein) pocket cavity sasurface 0;
Jmol Innovations: Surfaces
JVXL format
- compresses
surface data
up to 300:1
- enables webbased delivery
load 3dfr.pdb;isosurface “3dfr-cavity.jvxl” fullylit
Jmol Innovations: Surfaces
JVXL File sizes 27K (left), and 37K (right).
Jmol Innovations: Quaternion Frames
• The basic idea is that each amino acid residue can be
assigned a “frame” that describes its position and
orientation in space.
Jmol Innovations: Quaternion Frames
• A quaternion is a set of four numbers.
• Unit quaternions can describe rotations.
Jmol Innovations: Quaternion Frames
• The choice of frame is (seemingly) arbitrary.
“P”
“C”
“N”
Local Helical Axes
• The quaternion difference describes how one gets from
one frame to the next. This is the local helical axis.
Local Helical Axes
• The quaternion difference describes how one gets from
one frame to the next. This is the local helical axis.
Local Helical Axes
• Strings of local helical axes identify actual “helices.”
Local Helical Axes
• Sheet strands are also technically helical as well.
Local Helical Axes
Quaternion Difference Map
Quaternion Straightness
Quaternion Straightness
Bottom Line:
Visualization Can Drive Research
• Future directions:
– Natural extension to nucleic acids
– Define “motifs” based on quaternions
– Extension to molecular dynamics calculations and ligand binding
Bottom Line:
Visualization Can Drive Research
• Future directions:
– Natural extension to nucleic acids
– Define “motifs” based on quaternions
– Extension to molecular dynamics calculations and ligand binding
The Jmol Molecular Visualization Project
• Impact areas
Organic chemistry
(Small molecules; MO)
The Jmol Molecular Visualization Project
• Impact areas
Organic chemistry
(Small molecules; MO)
Biochemistry
(PDB/mmCIF; cartoons, cavities)
The Jmol Molecular Visualization Project
• Impact areas
Organic chemistry
(Small molecules; MO)
Inorganic chemistry
Biochemistry
(PDB/mmCIF; cartoons, cavities)
(CIF; point/space groups)
The Jmol Molecular Visualization Project
• Impact areas
Organic chemistry
(Small molecules; MO)
Inorganic chemistry
Biochemistry
(PDB/mmCIF; cartoons, cavities)
Material Science
(EM surfaces; surface layers)
(CIF; point/space groups)
The Jmol Molecular Visualization Project
• Impact areas
Organic chemistry
(Small molecules; MO)
Inorganic chemistry
Biochemistry
(CIF; point/space groups)
(PDB/mmCIF; cartoons, cavities)
Material Science
(EM surfaces; surface layers)
Computer Science
(OS Java algorithms;
surface compression)
The Jmol Molecular Visualization Project
• Impact areas
Organic chemistry
(Small molecules; MO)
Inorganic chemistry
Biochemistry
(CIF; point/space groups)
(PDB/mmCIF; cartoons, cavities)
Mathematics
(SAGE; quaternions)
Material Science
(EM surfaces; surface layers)
Computer Science
(OS Java algorithms;
surface compression)
The Jmol Molecular Visualization Project
• Impact areas
Organic chemistry
(Small molecules; MO)
Inorganic chemistry
(CIF; point/space groups)
Biochemistry
(PDB/mmCIF; cartoons, cavities)
Cheminformatics
(YOUR IDEA HERE)
Mathematics
(SAGE; quaternions)
Material Science
(EM surfaces; surface layers)
Computer Science
(OS Java algorithms;
surface compression)
Acknowledgments
• Dan Gezeltzer, Michael Howard, Egon Willighagen, Rene
Kanters, Nico Vervelle, and the whole Jmol development
team
• Dan Kohler ’09, Sean Johnston ’09, and Steven Braun ‘11
• Andrew Hanson, Indiana University
• Howard Hughes Medical Institute
• Jmol user community
• Brian Marsden
[email protected]
http://Jmol.sourceforge.net