Three-Layer Multiscale Approach Based on Extremely Localized Molecular Orbitals to Investigate Enzyme Reactions

Quantum mechanics/molecular mechanics (QM/MM) calculations are widely used embedding techniques to computationally investigate enzyme reactions. In most QM/MM computations, the quantum mechanical region is treated through density functional theory (DFT), which offers best compromise between chemical accuracy and computational cost. Nevertheless, obtain more accurate results, one should resort wave function-based methods, however lead a much larger cost already for relatively small QM subsystems. To overcome this drawback, we propose coupling of our QM/ELMO (quantum mechanics/extremely localized molecular orbital) approach with mechanics, thus introducing three-layer QM/ELMO/MM technique. The strategy an method in chemically relevant part system at level, while rest described frozen ELMOs. Since reproduces results fully computations within lower effort, it can be considered suitable extend range applicability scheme. paper, other than briefly presenting theoretical bases technique, will also discuss its validation on well-tested deprotonation acetyl coenzyme A by aspartate citrate synthase.