Structural basis for Roscovitine selectivity. The 3D structure of p38 (PDB 2GTM, wire rendering with grey carbons) was superposed onto the structure of CDK2 (hidden) in complex with Roscovitine (PDB 2A4L, ball and stick rendering with green carbons). Roscovitine appears to clash (orange lines) with Leu 167 (ball and stick rendering with grey carbons) of p38. Importantly, Leu 167 is buried deep in the pocket where there is little room to maneuver. In contrast, Ala 144 (stick rendering with green carbons) of CDK2 accommodates the compound. Based on this putative steric clash, we propose that S-Filter correctly predicted Ala 144 as specificity determinant for Roscovitine.