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

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• 作者：Lilian Olivieri^a ; ^b ; ^c ; ^d ; Fabrice Gardebien^a ; ^b ; ^c ; ^d ; ^{Fabrice.Gardebien@univ-reunion.fr" class="auth_mail}
• 关键词：CHARMM force field ; Parametrization ; High-affinity ligand ; FKBP12 ; Molecular mechanics
• 刊名：Journal of Molecular Graphics and Modelling
• 出版年：April, 2014
• 年：2014
• 卷：49
• 期：Complete
• 页码：118-128
• 全文大小：1975 K

文摘

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.