Format

Send to

Choose Destination
Proteins. 1997 Jul;28(3):313-24.

Mean field analysis of FKBP12 complexes with FK506 and rapamycin: implications for a role of crystallographic water molecules in molecular recognition and specificity.

Author information

1
Agouron Pharmaceuticals Inc., San Diego, California 92121, USA.

Abstract

Mean field analysis of FKBP12 complexes with FK506 and rapamycin has been performed by using structures obtained from molecular docking simulations on a simple, yet robust molecular recognition energy landscape. When crystallographic water molecules are included in the simulations as an extension of the FKBP12 protein surface, there is an appreciable stability gap between the energy of the native FKBP12-FK506 complex and energies of conformations with the "native-like" binding mode. By contrast, the energy spectrum of the FKBP12-rapamycin complex is dense regardless of the presence of the water molecules. The stability gap in the FKBP12-FK506 system is determined by two critical water molecules from the effector region that participate in a network of specific hydrogen bond interactions. This interaction pattern protects the integrity and precision of the composite ligand-protein effector surface in the binary FKBP12-FK506 complex and is preserved in the crystal structure of the FKBP12-FK506-calcineurin ternary complex. These features of the binding energy landscapes provide useful insights into specific and nonspecific aspects of FK506 and rapamycin recognition.

PMID:
9223178
[Indexed for MEDLINE]

Supplemental Content

Loading ...
Support Center