Fig. 4: Impact of conformation on ABFE calculations for HSP90.
From: Evaluating the use of absolute binding free energy in the fragment optimisation process
a Comparison of the structures of PDB IDs 2XHT (blue) and 2XDL (red) demonstrating the difference in helicity between the two models and b, c a zoomed view of the affected helix. Residues 100–124 have been highlighted in a darker colour to aid in visualisation. PDB ID 2XAB, which is similar in structure to 2XDL and 2XHX which is similar in structure to 2XHT are not shown. d Absolute binding free energies of the HSP90 ligands all starting from the 2XDL-like helix loop conformation. Free energy estimates are the means of the estimates across replicas, with error bars as their standard deviation. Correlation metrics calculated from the mean estimate values, with error bars derived from bootstrap resampling. All free energy results, including RMSE values, have units of kcal/mol.
