Mapping Enzymatic Catalysis using the Effective Fragment Molecular Orbital Method: Towards all ab initio Biochemistry

Abstract

We extend the Effective Fragment Molecular Orbital (EFMO) method to the frozen domain approach where only the geometry of an active part is optimized, while the many-body polarization effects are considered for the whole system. The new approach efficiently mapped out the entire reaction path of chorismate mutase in less than four days using 80 cores on 20 nodes, where the whole system containing 2398 atoms is treated in the ab initio fashion without using any force fields. The reaction path is constructed automatically with the only assumption of defining the reaction coordinate a priori. We determine the reaction barrier of chorismate mutase to be $18.3\pm 3.5$ kcal mol${}^{-1}$ for MP2/cc-pVDZ and $19.3\pm 3.6$ for MP2/cc-pVTZ in an ONIOM approach using EFMO-RHF/6-31G(d) for the high and low layers, respectively.

SI not attached

References in corpus (2)

• FragIt: A Tool to Prepare Input Files for Fragment Based Quantum Chemical Calculations
• The Effective Fragment Molecular Orbital Method for Fragments Connected by Covalent Bonds

Cited by in corpus (3)

• Multiple Time Step Integrators in Ab Initio Molecular Dynamics
• Hybrid RHF/MP2 geometry optimizations with the Effective Fragment Molecular Orbital Method
• Quantum computational study of chloride ion attack on chloromethane for chemical accuracy and quantum noise effects with UCCSD and k-UpCCGSD ansatzes