Molecular recognition mechanism of FK506 binding protein: An all-electron fragment molecular orbital study

摘要: The fragment molecular orbital (FMO) method has enabled electronic structure calculations and geometry optimizations of very large molecules with ab initio quality. We applied the to four FK506 binding protein (FKBP) complexes (denoted by their PDB codes 1fkb, 1fkf, 1fkg, 1fki) containing rapamycin, FK506, two synthetic ligands. geometries reduced complex models were optimized at restricted Hartree-Fock (FMO-RHF) level using 3-21G basis set, then for a better estimate binding, energetics refined higher theory (2nd order Moller-Plesset perturbation FMO-MP2 6-31G* set). Thus, obtained energies -103.9 (-82.0), -102.2 (-69.2), -70.1 (-57.7), -71.3 (-55.3) kcal/mol 1fki, respectively, where correlation contribution is given in parentheses. results show that electron extremely important, it accounts 70-80% energy. recognition mechanism FKBP was analyzed detail based on FMO-pair interactions between residues Solvation effects protein-ligand estimated Poisson-Boltzmann/surface area model.