Hybrid RHF/MP2 geometry optimizations with the effective fragment molecular orbital method

Area of Science:

• Computational Chemistry
• Quantum Chemistry
• Biophysical Chemistry

Background:

• The frozen domain effective fragment molecular orbital (FD-EFMO) method is a powerful tool for studying large molecular systems.
• Accurate treatment of electron correlation is crucial for understanding reaction mechanisms and transition states in enzymatic catalysis.

Purpose of the Study:

• To extend the FD-EFMO method to incorporate the MP2 (Møller–Plesset perturbation theory) level of theory for a single fragment.
• To apply this enhanced method to investigate the enzymatic conversion of chorismate to prephenate catalyzed by Chorismate Mutase.

Main Methods:

• The modified FD-EFMO method treats a single fragment (the substrate) at the MP2 level while the rest of the system is treated at the RHF (Restricted Hartree–Fock) level.
• The approach was tested on the chorismate to prephenate conversion, a key reaction in amino acid biosynthesis.
• Geometry optimizations were performed using both RHF and MP2 levels for comparison.

Main Results:

• MP2 geometry optimization of the substrate significantly lowered the activation barrier by up to 3.5 kcal/mol compared to RHF optimizations.
• The MP2 treatment led to smoother convergence of the reaction profile with respect to the basis set size.
• A moderate increase in computational cost (approximately a factor of two for double zeta basis sets) was observed relative to RHF calculations.

Conclusions:

• The extended FD-EFMO method with MP2 treatment for key fragments provides a more accurate description of enzymatic reaction barriers.
• This approach offers a computationally feasible way to achieve higher accuracy for complex biochemical systems.
• The findings suggest potential for broader application in studying enzyme mechanisms and designing inhibitors.