The Find Binding Pockets algorithm

The same algorithm is used to find binding pockets in the Find Binding Pockets tool and in the Setup Binding Site dialog box. In the case of the Find Binding Pockets tool, the target is all protein chains in the Molecule Project combined. In the case of the Setup Binding Site dialog box, the target is all molecules included in the binding site setup. First, a discrete 3D grid with a resolution of 0.8 Å, covering all target molecules, is created. At every grid point, a sphere is placed with a radius of 1.4 Å. If this sphere overlaps with any of the target atoms (represented by their van der Waals radii), the grid point is part of the inaccessible volume. All other points are referred to as accessible.

Second, each accessible grid point is checked to see whether it is part of a pocket, using the following procedure. 16 directions are selected uniformly, and these are followed away from the point (see the red and orange lines in the 2D example depicted in figure 10.64). If an inaccessible grid point is hit, before hitting the grid boundary, it is registered. If more than 12 of the directions hit inaccessible volume (or only 8, if the option "Include more exposed pockets" is selected in the "Find Binding Pockets" tool wizard), then the point is marked as being part of a pocket (visualized as green or blue dots in the 3D view).

Image 2D_pocket_finder_algorithm
Figure 10.64: 2D schematic of the Find Binding Pockets algorithm. The blue area represents the target, and all grid points covered in blue are inaccessible. The probe directions are indicated for both a pocket point (red lines) and an exposed point (orange lines). Green dots indicate pocket points.

The final step is to group the neighboring grid points to form the individual pockets. The volume of a pocket is then estimated as the number of grid points belonging to the pocket times the volume of a unit grid cell. It is typically only relevant to see the largest pockets, and the smaller pockets can safely be ignored. The "Ignore pockets with volumes (Å3) less than" option in the "Find Binding Pockets" wizard, thus specifies the limit for discarding the smallest pockets found. When binding pockets are found in the Binding Site Setup, all pockets with volume less than 10 Å3 are discarded.