ROCS shape query sources¶
ROCS is most commonly used to compare alignments of molecular shapes. However, a range of other shapes, e.g. molecular grids, form equally valid and useful alignment target queries, with the following provisos.
Grids are built without color atoms. The absence of color atoms in a query usually causes ROCS performance to be lower. For ligand shape queries adding color atoms has been shown to enhance ROCS performance with twice as much signal over random when color atoms are used, compared to shape alone. Without color the ROCS TanimotoCombo scores will also generally be lower (TanimotoCombo 0-1 instead of 0-2). Therefore, one should either add color atoms manually to a grid-based query (see section Editing ROCS queries in vROCS) or compare with the ShapeTanimoto score obtained from a ligand-shape query.
Using DUD 1.0 with ROCS shape only the average AUC across the 38 cases is approximately 0.6. With shape + color the average AUC is around 0.73. Therefore, the delta over random for shape is 0.1 and for shape + color is 0.23. Hence, by this rather odd way of looking at it there is twice as much signal. - P. Hawkins, OpenEye
It is possible to add color points to grid shapes using the editing tools available in vROCS, described in the tutorial Building and editing a query manually and this can usefully guide the alignments. However, ligand shape with color generally provides superior results to using a grid-based query. Grids can be useful in cases where no suitable ligand query exists.
There are several potential sources of grids:
AFITT can produce a grid of electron density from crystallographic data. It is also possible to back-compute a grid of density for a crystallographic or docked ligand. This allows heavier atoms to contribute more to the grid than light ones, whereas shape grids are uniform.
Spicoli will make grids from surfaces.
OEDocking also produces a shape grid.
Using the OEGrid toolkit you can read in any grid format and, using an ASCII interchange format, write it to an OE format that could be used by vROCS. This capability allows access to grids produced by third party applications. For example, DOCK ([DOCK]) uses scoring grids, GRID ([GRID]) makes grids and so on. All of these could be used to makes queries for vROCS, but their application and usefulness has not been thoroughly validated.
Recent research has been carried out at OpenEye to validate some tools currently under development ([Nicholls-2010]). These produce shapes that describe a protein binding pocket (using the same technology as Spicoli) for use as ROCS queries. Initial results show that shapes from sources other than pure ligands can be successfully used as useful ROCS queries and that adding color atoms is often useful to increase selectivity (and is never detrimental, to date), just as for ligand-based shape and color queries.