Fig. 2.

Representation of the FES of the 3b binding process to ADA with the three main minima shown as insets, (A, B and C). The FES is represented as function of the distance and dihedral CVs using isosurfaces of 1 kcal/mol. It is important to underline that no bias has been added to the dihedral CV and the statistics collected during the metadynamics simulations on the torsion CV is used to generate the final FES using the reweighting protocol (31). In the insets the ligand and the main interacting residues are displayed as licorice while the protein is represented as cartoon with the H3 α-helix colored in yellow. The ligand/Asp19 water bridge interaction is also shown while only polar hydrogens interacting with the ligand are displayed for clarity.