Table 2.

Summary of cofactors and cofactor analogs investigated in this work.

Name	No. of PDB entries	Protein names: No. of high-quality conformers	No. of Confs.a	Major observations
Sinefungin (SFG)	70	Methyltransferase: 23 Others: 7	6	Three clusters of conformers are observed. The largest group includes 23 highly similar conformers and includes structures bound to proteins that share low sequence identity. The maximum RMSD measured for any of the sinefungin conformers is 3.6 Å
S-adenosylmethionine (SAM)	410	Methyltransferase: 92 Others: 31	24	A wide variety of conformations are observed, with a clear clustering into three distinct groups of conformers. Within these groups, a large number of similar conformers are observed, even when bound to proteins sharing low sequence identity. The maximum pairwise RMSD is 3.3 Å
S-Adenosyl-L-Homocysteine (SAH)	784	Methyltransferase: 284 RNA polymerase: 8 Others: 19	23
Glutathione (GSH)	360	Glutathione transferase: 46 Others: 28	16	Most of the conformers have a pairwise RMSD between 0.6 and 1.6 Å, but the maximum pairwise RMSD is 3.6 Å
Adenosine monophosphate (AMP)	575	Total: 171	36	A wide variety of different conformers is observed. One distinct, extremely coiled conformer was observed in complex with an adenylate kinase-related protein. The maximum pairwise RMSD is 2.5 Å
Adenosine diphosphate (ADP)	1,810	Total: 462	81	The conformers are similar to those observed for AMP, despite the presence of an additional phosphate group. The median RMSD is 0.9 Å
Adenosine triphosphate (ATP)	1,079	Total: 218	76	ATP is observed in an extended conformation in most structures, but some conformers are extremely bent. The median and the maximum pairwise RMSDs are 1.6 and 3.9 Å, respectively
Flavin mononucleotide (FMN)	919	Total: 367	21	The overall median RMSD is 0.9. The all-against-all comparison revealed four groups of conformers, with peaks in the RMSD distribution at around 0.3, 1.2, 1.7, and 2.4 Å

^aNo. of distinct bioactive conformations.