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

Area of Science:

• Computational chemistry
• Quantum chemistry
• Biochemistry

Background:

• Molecular Fractionation with Conjugate Caps (MFCC) is widely used for quantum-chemical protein analysis.
• MFCC overlooks crucial interactions between amino acid fragments, like hydrogen bonds, limiting accuracy.
• Accurate modeling of protein interactions is vital for understanding biological function.

Purpose of the Study:

• To develop an enhanced fragmentation method for quantum-chemical protein calculations.
• To incorporate inter-fragment interactions into the MFCC scheme.
• To improve the accuracy of energy predictions for proteins and polypeptides.

Main Methods:

• Combining the Molecular Fractionation with Conjugate Caps (MFCC) method with a second-order many-body expansion (MBE).
• The MFCC-MBE(2) scheme systematically includes all fragment-fragment, fragment-cap, and cap-cap interactions.
• Validation using selected polypeptides and proteins to assess energy prediction accuracy.

Main Results:

• The MFCC-MBE(2) scheme significantly reduces errors in total protein energies, by up to one order of magnitude.
• Accurate prediction of relative energies for different protein conformers was achieved.
• The method retains the simplicity and chemically meaningful fragments of the original MFCC scheme.

Conclusions:

• The MFCC-MBE(2) method offers a substantial improvement over standard MFCC for quantum-chemical protein studies.
• This approach provides a more accurate and reliable way to calculate protein energies.
• The enhanced method facilitates deeper insights into protein structure-function relationships through precise energy calculations.