Comparison of druggability estimations on known flexible protein pockets.

Targets are from Huang and Jacobson[17], and include all targets where at least two structures have an RMSDave greater than 1.5 Å. The data under the Structural data and Docking-based druggability are from reference 17. RMSDave is the RMSD of side-chains in the binding site within 4.5 Å of crystallographic ligands.[17]Variation is calculated as the difference between the largest and smallest druggability score values divided by the average of all druggability score values for the particular target. The flexible druggability method is only performed for binding sites that meet an initial score (with the rigid crystal structure). However, for the purposes of this comparison study, we removed this cut-off in order to generate values for IL-2 and HPV E2. For IL-2, performing the flexibility modeling procedure results in DScore+ values of 1.5 (1z92), 1.5 (1py2), and 1.7 (1m48), with small, non-drug-like volumes of 98, 82, and 53 Å3, respectively. For HPV E2, the DScore+ values are 1.1 (1tue) and 1.5 (1r6n), with reasonable drug-like volumes. Calculations on all targets from reference 17 are included as S4.