The full electron structure of the FKBP12/FK506 complex.
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.
a Department of Computer Science and Engineering , Oakland University , 129 Dodge Hall of Engineering, 2200 N. Squirrel Road, Rochester 48309-4401 , MI , USA.
Allison M
AM
Rossetto
Wenjin
W
Zhou
Xiaodong
X
Pang
Linxiang
L
Zhou
D020816:Amino Acid Motifs; D001665:Binding Sites; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016559:Tacrolimus / Q000737:chemistry*; D022061:Tacrolimus Binding Protein 1A / Q000737:chemistry*; D013816:Thermodynamics
D007166:Immunosuppressive Agents; D022061:Tacrolimus Binding Protein 1A; D016559:Tacrolimus
FKBP12/FK506; activity atoms; activity residues; frontier orbital; full electron structure