Download IsoStar User Guide and Tutorials 2010 Release

6
Experimental Details and Limitations
6.1 Details of Scatterplot Methodology
6.1.1 Structures Used for Calculating CSD-Based Scatterplots
• The Cambridge Structural Database (CSD; http://www.ccdc.cam.ac.uk/products/csd/) contains
the results of organic and metallo-organic crystal structure determinations. Standard software
(ConQuest) can be used to search the database for intermolecular contacts between any specified
pair of chemical groups.
• If the structure of a compound occurs more than once in the CSD (duplicate structure
determinations of the same crystal form or determinations of different crystal forms), only one
example is included in the searches used to set up the IsoStar scatterplots.
• With this exception, all CSD structures are used for the IsoStar searches, regardless of
crystallographic R-factor, presence of disorder, etc. However, CSD structures with missing
hydrogen atoms are not used in creating IsoStar scatterplots unless the missing hydrogen atoms
are irrelevant to the plot (i.e. not part of either the central or contact group).
6.1.2 Structures Used for Calculating PDB-Based Scatterplots
• The Protein Data Bank (PDB; http://www.rcsb.org/pdb/) contains the results of protein
structures, including many protein-ligand complexes. Only protein-ligand, ligand-water and
protein-water contacts are included in IsoStar scatterplots, i.e. contacts between protein atoms
are ignored.
• A subset of the database is used for IsoStar. Amongst the restrictions applied are:
• Crystallographic determinations only (no NMR structures).
• Resolution less than or equal to 2.5Å.
• Protein-ligand complexes only. A ligand is defined as a peptide of up to ten residues or a nonpeptide or non-haem molecule of at least nine atoms.
• DNA and RNA complexes excluded.
• Most covalently-bonded complexes excluded.
• Most duplicate and near-duplicate structures excluded (e.g. structures with the words mutant,
mutation or mutated in their PDB files).
• No ligands with atoms of partial occupancy.
• For structures containing more than one binding site with the same ligand, only one of the
binding sites is used.
• To generate the IsoStar plots, ligands of interest and their surrounding residues (ie. binding sites)
are identified in all structures. Crystallographic symmetry operators are applied to generate the
full ligand environment where appropriate.
• In addition, a few structures have been eliminated because they caused processing problems.
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IsoStar User Guide