SiteMap Hydrophobic Map

The quantity representing hydrophobicity is constructed by adding an “electric-field penalty” (positive) term to the van der Waals term:

Grid_phobic = vdW_energy − 0.30 * oriented-dipole_energy

Hydrophobic regions thus are regions where something would like to be, but water would not. The starting point for defining the hydrophobic regions is to consider the regions within which the sum of the two terms is more negative than a given threshold.

SiteMap offers several alternatives for the definition of hydrophobic regions. The least restrictive definition uses a threshold of −0.75 kcal/mol, and includes all site points that lie within this region. This is not the default behavior, but represents the original SiteMap definition. The more restrictive definitions involve two possible modifications to the hydrophobic region.

In the first, grid points that border on too many assigned philic points, that have too few phobic-point or “inside-protein” neighbors, or that border on too many free-space “outside” points are reclassified as non-phobic.

In the second, for each phobic grid point the fraction of radial rays that intersect the protein surface within a given distance (default 6 Å) is calculated, and the phobic potential is then multiplied by this fraction. By scaling down the phobic potential, exposed regions are less favored than regions that are sheltered from the solvent, like the Glide XP detection of “phobic enclosure” [7]. The threshold for defining the phobic region is also reduced, to −0.50 kcal/mol. This modification considers the nature of the site beyond the immediate vicinity of the grid point, in a way that the first modification cannot.

The default behavior is to include both of these modifications.