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

Abstract

AbstractThe 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.