A Projector-Embedding Approach for Multiscale Coupled-Cluster Calculations Applied to Citrate Synthase

Area of Science:

• Computational chemistry
• Biomolecular modeling

Background:

• Projector-based embedding is a robust multiscale method for electronic molecular properties.
• Quantum mechanics/molecular mechanics (QM/MM) is widely used for enzyme-catalyzed reactions.

Purpose of the Study:

• Couple projector embedding with QM/MM for enzyme-catalyzed reactions.
• Calculate accurate energy profiles for proton abstraction by citrate synthase.

Main Methods:

• Utilize projector-based embedding combining coupled-cluster, density-functional theory (DFT), and molecular mechanics.
• Embed correlated ab initio methods within DFT to mitigate functional sensitivity.

Main Results:

• Successfully applied projector embedding with QM/MM to an enzyme-catalyzed reaction.
• Obtained high-accuracy energy profiles for proton abstraction from acetyl-coenzyme A.

Conclusions:

• Projector-based embedding offers a straightforward and accurate approach for QM/MM studies of enzyme reactions.
• This method eliminates functional sensitivity in DFT calculations for complex systems.