Classical force field parameters for two high-affinity ligands of FKBP12

• We determine the force field parameters for two ligands.
• Two high-affinity ligands of FKBP12 are considered.
• Fitting procedure is based on quantum chemical calculations.
• Attention is paid to the numerous dihedral angles of the ligands.

FKBP12 is an important target in the treatment of transplant rejection and is also a promising target for cancer and neurodegenerative diseases. We determined for two ligands of nanomolar affinity the set of parameters in the CHARMM force field. The fitting procedure was based on reproducing the quantum chemistry data (distances, angles, and energies). Since the dynamical behavior of such ligands strongly depends on the dihedral angles, care was taken to derive the corresponding parameters. Moreover, since each of the central core region of these two ligands is similar to other known ligands or drugs of other proteins, part at least of these parameters could also be useful for these other ligands.

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