Jmol and its Potential for Data Mining and Molecular Visualization in Drug Discovery

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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

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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

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The Jmol Community

• Professional graphics designers
• Professional developers
• Bioinformatics/Cheminformatics Professionals
• Professors, graduate students, undergraduates

• Generally one of three focal points
• Research
• Publishing
• Education

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The Jmol Community

• Professional graphics designers
• Professional developers
• Bioinformatics/Cheminformatics Professionals
• Professors, graduate students, undergraduates

• Common Goals
• Communication
• Web-based delivery

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Jmol History

• Jmol version 9 (2004)
• Chime replacement
• Small molecules
• Minimal functionality

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Jmol History

• Jmol version 10 (2005)
• better graphics
• Chime/RasMol
• replacement
• more functionality

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Jmol History

• Jmol version 11.0 (2007)
• surfaces
• crystallographic symmetry

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Jmol History

• Jmol version 11.2 (2007)
• Jmol version 11.4 (2008)
• Jmol version 11.6 (2008)
• better perspective model
• navigation mode
• better graphics
• export to POV-Ray, VRML
• signed applet
• extensive scripting

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Jmol History

• Jmol version 11.8 (2009)
• Jmol version 11.9 (2009)
• data-mining mode
• quaternion-based analysis
• live images
• Jmol consolidated file format

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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.

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Jmol Innovations Surfaces
load 3dfr.pdbisosurface select(protein) ignore
(not solvent and not protein) pocket cavity
sasurface 0
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Jmol Innovations Surfaces
JVXL format - compresses surface data
up to 3001 - enables web- based delivery
load 3dfr.pdbisosurface 3dfr-cavity.jvxl
fullylit
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Jmol Innovations Surfaces
JVXL File sizes 27K (left), and 37K (right).
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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.

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Jmol Innovations Quaternion Frames

• A quaternion is a set of four numbers.
• Unit quaternions can describe rotations.

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Jmol Innovations Quaternion Frames

• The choice of frame is (seemingly) arbitrary.
• P C
  N

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Local Helical Axes

• The quaternion difference describes how one gets
  from one frame to the next. This is the local
  helical axis.

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Local Helical Axes

• The quaternion difference describes how one gets
  from one frame to the next. This is the local
  helical axis.

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Local Helical Axes

• Strings of local helical axes identify actual
  helices.

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Local Helical Axes

• Sheet strands are also technically helical as
  well.

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Local Helical Axes
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Quaternion Difference Map
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Quaternion Straightness
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Quaternion Straightness
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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

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Bottom LineVisualization Can Drive Research

• Future directions
• Natural extension to nucleic acids
• Define motifs based on quaternions
• Extension to molecular dynamics calculations and
  ligand binding

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The Jmol Molecular Visualization Project

• Impact areas

Organic chemistry (Small molecules MO)
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The Jmol Molecular Visualization Project

• Impact areas

Organic chemistry (Small molecules MO)
Biochemistry (PDB/mmCIF
cartoons, cavities)
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The Jmol Molecular Visualization Project

• Impact areas

Organic chemistry (Small molecules MO)
Inorganic chemistry (CIF point/space groups)
Biochemistry (PDB/mmCIF
cartoons, cavities)
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The Jmol Molecular Visualization Project

• Impact areas

Organic chemistry (Small molecules MO)
Inorganic chemistry (CIF point/space groups)
Biochemistry (PDB/mmCIF
cartoons, cavities)
Material Science (EM surfaces surface
layers)
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The Jmol Molecular Visualization Project

• Impact areas

Organic chemistry (Small molecules MO)
Inorganic chemistry (CIF point/space groups)
Biochemistry (PDB/mmCIF
cartoons, cavities)
Material Science (EM surfaces surface
layers)
Computer Science (OS Java algorithms
surface compression)
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The Jmol Molecular Visualization Project

• Impact areas

Organic chemistry (Small molecules MO)
Inorganic chemistry (CIF point/space groups)
Biochemistry (PDB/mmCIF
cartoons, cavities)
Mathematics (SAGE quaternions)
Material Science (EM surfaces surface
layers)
Computer Science (OS Java algorithms
surface compression)
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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)
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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
• hansonr_at_stolaf.edu
• http//Jmol.sourceforge.net