Figure 1.

(a)- Description of Surface Atom Determination by SACA method. Enclose the protein in a box and emit rays from Center of Mass (COM). A surface atom is defined as the furthest atom from COM that intersects the ray (dashed lines). For each ray define a sphere from COM with diameter from the furthest atomic pair. Randomly chose a test particle within the sphere and emit rays to find the remaining surface atoms (blue and orange lines). Repeat the procedure until no new surface atoms found. (b)- Definition of Span. Spherical cavities overlap if the distance between their centers is less than the sum of their diameters (left). Overlapping cavities are grouped into clusters (right). The linear distance between two furthest cavities in a cluster is called span (red solid line).