Jmol and its Potential for Data Mining and Molecular Visualization in Drug Discovery Robert M. Hanson Department of Chemistry, St. Olaf College Northfield, MN 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 Professional graphics designers Professional developers Bioinformatics/Cheminformatics Professionals Professors, graduate students, undergraduates Generally one of three focal points: –Research –Publishing –Education

The Jmol Community 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) –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) –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 load 3dfr.pdb;isosurface “3dfr-cavity.jvxl” fullylit JVXL format - compresses surface data up to 300:1 - enables web- based delivery

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

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) Biochemistry (PDB/mmCIF; cartoons, cavities) Inorganic chemistry (CIF; point/space groups)

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

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

The Jmol Molecular Visualization Project Impact areas Organic chemistry (Small molecules; MO) Biochemistry (PDB/mmCIF; cartoons, cavities) Inorganic chemistry (CIF; point/space groups) Material Science (EM surfaces; surface layers) Mathematics (SAGE; quaternions) Cheminformatics (YOUR IDEA HERE) 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