A simple and consistent quantum-chemical fragmentation scheme for proteins that includes two-body contributions.

The Molecular Fractionation with Conjugate Caps (MFCC) method is a popular fragmentation method for the quantum-chemical treatment of proteins. However, it does not account for interactions between the amino acid fragments, such as intramolecular hydrogen bonding. Here, we present a combination of the MFCC fragmentation scheme with a second-order many-body expansion (MBE) that consistently accounts for all fragment-fragment, fragment-cap, and cap-cap interactions, while retaining the overall simplicity of the MFCC scheme with its chemically meaningful fragments. We show that with the resulting MFCC-MBE(2) scheme, the errors in the total energies of selected polypeptides and proteins can be reduced by up to one order of magnitude and relative energies of different protein conformers can be predicted accurately.

Accurate quantum-chemical fragmentation calculations for ion-water clusters with the density-based many-body expansion.

The many-body expansion (MBE) provides an attractive fragmentation method for the efficient quantum-chemical treatment of molecular clusters. However, its convergence with the many-body order is generally slow for molecular clusters that exhibit large intermolecular polarization effects. Ion-water clusters are thus a particularly challenging test case for quantum-chemical fragmentation methods based on the MBE. Here, we assess the accuracy of both the conventional, energy-based MBE and the recently developed density-based MBE [Schmitt-Monreal and Jacob, Int. J. Quantum Chem., 2020, 120, e26228] for ion-water clusters. As test cases, we consider hydrated Ca2+, F-, OH-, and H3O+, and compare both total interaction energies and the relative interaction energies of different structural isomers. We show that an embedded density-based two-body expansion yields highly accurate results compared to supermolecular calculations. Already at the two-body level, the density-based MBE clearly outperforms a conventional, energy-based embedded three-body expansion. We compare different embedding schemes and find that a relaxed frozen-density embedding potential yields the most accurate results. This opens the door to accurate and efficient quantum-chemical calculations for large ion-water clusters as well as condensed-phase systems.