The full electron structure of the FKBP12/FK506 complex

Abstract

We present a study of FKBP12/FK506 using an electron structure calculation. These calculations employ a novel technique called eCADD on the protein’s full electron structure along with its hydrophobic pocket and the frontier-orbital-perturbation theory. We first obtain the energy bands and orbital coefficients of protein FKBP12. On this basis, we found that the activity atoms and activity residues of FKBP12 were in good agreement with X-ray crystallography experiments. The results indicate that the interactions occur only between the LUMOs of FKBP12 and the HOMO of FK506, not between the HOMOs of FKBP12 and the LUMO of FK506. In other words, the activity sites of protein FKBP12 are located on its LUMOs, not HOMOs. The electron structures of FKBP12/FK506 give us a clearer understanding of their interaction mechanism and will help us design new ligands of FKBP12.

Keywords:

• FKBP12/FK506
• full electron structure
• frontier orbital
• activity residues
• activity atoms

Acknowledgement

The authors thank Professor Yuanjie Ye for his kind help, Dr Kaillathe Padmanadhan, Department of Biochemistry, Michigan State University, for providing the SGI machine and the Department of Computer Science at Oakland University for providing the Linux cluster.