Lundberg Marcus, Morokuma Keiji
Fukui Institute for Fundamental Chemistry, Kyoto University, 34-4 Takano Nishihiraki-cho, Sakyo, Kyoto 606-8103, Japan.
J Phys Chem B. 2007 Aug 9;111(31):9380-9. doi: 10.1021/jp071878g. Epub 2007 Jul 19.
Binding of dioxygen to a non-heme enzyme has been modeled using the ONIOM combined quantum mechanical/molecular mechanical (QM/MM) method. For the present system, isopenicillin N synthase (IPNS), binding of dioxygen is stabilized by 8-10 kcal/mol for a QM:MM (B3LYP:Amber) protein model compared to a quantum mechanical model of the active site only. In the protein system, the free energy change of O2 binding is close to zero. Two major factors consistently stabilize O2 binding. The first effect, evaluated at the QM level, originates from a change in coordination geometry of the iron center. The active-site model artificially favors the deoxy state (O2 not bound) because it allows too-large rearrangements of the five-coordinate iron site. This error is corrected when the protein is included. The corresponding effect on binding energies is 3-6 kcal/mol, depending on the coordination mode of O2 (side-on or end-on). The second major factor that stabilizes O2 binding is van der Waals interactions between dioxygen and the surrounding enzyme. These interactions, 3-4 kcal/mol at the MM level, are neglected in models that include only the active site. Polarization of the active site by surrounding amino acids does not have a significant effect on the binding energy in the present system.
已使用ONIOM组合量子力学/分子力学（QM/MM）方法对双原子氧与非血红素酶的结合进行了模拟。对于当前系统，异青霉素N合酶（IPNS），与仅活性位点的量子力学模型相比，对于QM:MM（B3LYP:Amber）蛋白质模型，双原子氧的结合稳定了8-10千卡/摩尔。在蛋白质系统中，O2结合的自由能变化接近于零。有两个主要因素持续稳定O2结合。第一个效应，在QM水平评估，源于铁中心配位几何结构的变化。活性位点模型人为地有利于脱氧状态（O2未结合），因为它允许五配位铁位点发生过大的重排。当包含蛋白质时，这个错误会被纠正。根据O2的配位模式（侧接或端接），对结合能的相应影响为3-6千卡/摩尔。稳定O2结合的第二个主要因素是双原子氧与周围酶之间的范德华相互作用。这些相互作用在MM水平为3-4千卡/摩尔，在仅包括活性位点的模型中被忽略。周围氨基酸对活性位点的极化在本系统中对结合能没有显著影响。
