Figure 11.

Three site MSLD system MCL1–7. Panel a shows the core ligand with two sites of substitutions, and the corresponding substituents. Panel b displays the calculated ΔΔG values for 58 out of 64 combinatorial ligands, with red bars indicating ligands for which experimental data is available. Panel c displays the calculated vs. experimental absolute binding free energies. Panel d displays binding free energies calculated using the additive approximation. Calculated relative free energies were converted to absolute by adding a constant offset value that minimizes errors associated with the choice of a single reference ligand as described in Methods. AUE are indicated on bottom right. Units are kcal/mol.