Structural basis for Fasudil selectivity. The 3D structure of PKA (PDB 1Q8T, wire rendering with grey carbons) superposed onto the structure of Rock1 (hidden) in complex with Fasudil (PDB 2ESM, ball and stick rendering with green carbons). Ala 215 (Stick rendering with green carbons) of Rock1 is smaller than Thr 183 (ball and stick rendering with grey carbons) of PKA which protrudes the pocket of ROCK (mustard surface). By mutating Thr 183 in PKA to the corresponding position in Rock (Ala 215), Bonn et al demonstrated that Fasudil inhibited the mutant PKA at levels similar to ROCK . The smaller residue was proposed by Bonn et al to allow Fasudil deeper access to the active site. Based on the above observations, we conclude that S-Filter correctly predicted Ala 215 as a specificity determinant.