title: Classical force field parameters for two high-affinity ligands of FKBP12.
abstract: 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.
authors.affiliation: DSIMB, INSERM, U1134, Paris F-75015, France; Université de la Réunion, UMR_S 1134, Faculté des Sciences et Technologies, 15, avenue René Cassin, BP 7151, 97715 Saint Denis Messag Cedex 09, Réunion; Institut National de la Transfusion Sanguine, F-75015 Paris, France; Laboratory of Excellence GR-Ex.
authors.forename: Lilian
authors.initials: L
authors.lastname: Olivieri
authors.affiliation: DSIMB, INSERM, U1134, Paris F-75015, France; Université de la Réunion, UMR_S 1134, Faculté des Sciences et Technologies, 15, avenue René Cassin, BP 7151, 97715 Saint Denis Messag Cedex 09, Réunion; Institut National de la Transfusion Sanguine, F-75015 Paris, France; Laboratory of Excellence GR-Ex. Electronic address: Fabrice.Gardebien@univ-reunion.fr.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Gardebien
mesh_terms: D000465:Algorithms; D008958:Models, Molecular; D022061:Tacrolimus Binding Protein 1A / Q000737:chemistry* / Q000378:metabolism
chemical_list: D022061:Tacrolimus Binding Protein 1A
keywords: CHARMM force field; FKBP12; High-affinity ligand; Molecular mechanics; Parametrization