Table 1.

Performance of various MD simulations in reproducing holo-like conformations of the protein structures (only C_α atoms) and of the putative binding sites (all non-hydrogenous atoms) considered in this work, measured by the percentage of structures with RSMD values below 2 and 2.5 Å, respectively. Results refer to the cumulative trajectories and to cluster representatives of both the standard MD simulation (MD_std) and the gEDES approach. PDB codes of each reference holo-structure are reported in the second row. The lowest value of the RMSD is reported in parentheses. Structural alignment for RMSD calculations has been performed on the region specified in the third row of each column.

	RMSD < 2 / 2.5 Å [%] (RMSDmin)
	Holo: 1AKE			Holo: 2ECK	Holo: 1ANK	Holo: 6F7U
	BSCOACH	BSAP5	Protein (Cα)	BSADP	BSAMP	BSGCP	Protein (Cα)
MDstd	0 / 0 (3.7)	0 / 0 (3.9)	0 / 0 (2.9)	0.04 / 1.9 (1.5)	0 / 0 (3.1)	8.5 / 23.5 (1.1)	4.4 / 16.2 (0.9)
gEDES	0.001 / 1.3 (2.0)	0.001 / 0.7 (2.0)	0.05 / 0.3 (1.8)	0.01 / 0.02 (0.9)	0 / 0.007 (2.2)	3.2 / 19.8 (1.3)	3.9 / 10.1 (1.0)
${\text{MD}}_{\text{std}}^{\text{clust}}$	0 / 0 (3.9)	0 / 0 (4.0)	0 / 0 (3.1)	0 / 1.8 (2.1)	0 / 0 (3.8)	11.2 / 24.2 (1.1)	3.1 / 16.8 (1.5)
gEDESclust	0.8 / 4.0 (2.0)	0 / 3.8 (2.2)	0 / 0.8 (2.1)	2.3 / 13.6 (1.1)	0 / 1.5 (2.2)	1.6 / 16.7 (2.0)	0.8 / 3.8 (2.0)