Table 2.

RMSD values were computed for each pair of homology model structures in our ensemble. The average RMSD was 1.27 Angstroms. The maximum RMSD was 1.675 Angstroms. This is close to the length of an alkane bond (1.54 Angstroms), and less than what is considered good resolution for a protein crystal structure (2.4 Angstroms).

Template 1	Template 2	RMSD	Pocket Score1
105E	2ANY	1.350	−11.63
1O5E	4NA8	1.675	−9.25
1O5E	5CE1	0.648	−7.94
1O5E	5TJX	1.527	−8.90
1O5E	6O1G	1.565	−7.47
1O5E	3W94	1.144	−6.26
2ANY	4NA8	1.136	−9.71
2ANY	5CE1	1.337	−10.13
2ANY	5TJX	0.923	−10.84
2ANY	6O1G	1.086	−9.19
2ANY	3W94	1.252	−6.96
4NA8	5CE1	1.582	−9.51
4NA8	5TJX	0.979	−9.18
4NA8	6O1G	1.055	−7.59
4NA8	3W94	1.558	−6.89
5CE1	5TJX	1.322	−8.92
5CE1	6O1G	1.561	−7.94
5CE1	3W94	1.127	−7.42
5TJX	6O1G	0.955	−9.35
5TJX	3W94	1.454	−8.32
6O1G	3W94	1.515	−6.84

¹PocketFeature computes the similarity of binding sites by comparing sets of protein microenvironments [15]. Scores below −4.0 indicate very high similarity (Supplementary Figure 2). Highly similar pockets are likely to bind the same ligands. We have previously used PocketFeature to identify novel off-target activity of kinase inhibitors and SERMs [15,17]. Here we use it to assess the similarity of homology model binding sites. The binding sites of our homology models exhibit extremely high similarity in a range which is typically observed for different crystal structures of the same protein.