Does the DFT Self-Interaction Error Affect Energies Calculated in Proteins with Large QM Systems?

Area of Science:

• Computational Chemistry
• Quantum Mechanics
• Molecular Modeling

Background:

• Self-interaction error is a known issue in density-functional theory (DFT) calculations.
• This error can significantly impact the accuracy of calculated energies, especially in large molecular systems with charged groups.
• Understanding and mitigating this error is crucial for reliable computational chemistry studies.

Purpose of the Study:

• To investigate the impact of self-interaction error in DFT on energy calculations for large systems (600-1000 atoms) with charged groups.
• To evaluate the performance of various quantum mechanical (QM) methods, including DFT functionals, in handling charge delocalization and environmental effects.
• To identify reliable computational methods for studying reaction and activation energies in complex molecular systems.

Main Methods:

• Employed 18 different quantum mechanical (QM) methods, including Hartree-Fock, pure, hybrid, and range-separated DFT functionals.
• Calculated reaction and activation energies for three protein models.
• Simulated different environments: vacuum, point-charge surrounding, and continuum-solvent model.
• Analyzed charge delocalization using Mulliken charges.

Main Results:

• Pure DFT functionals exhibited significant charge delocalization (∼0.1 e) in charged protein groups, affecting calculated energies.
• This charge delocalization led to inaccuracies when assessing the influence of the molecular surroundings.
• Hybrid DFT methods (CAM-B3LYP, BHLYP, M06-2X) showed good agreement (within kJ/mol) for energies, particularly in point-charge environments.

Conclusions:

• Pure DFT functionals are not recommended for large QM systems due to self-interaction error-induced charge delocalization.
• Hybrid DFT methods like CAM-B3LYP, BHLYP, and M06-2X are suitable for estimating environmental effects in large QM systems.
• These recommended methods provide reliable energy calculations, enabling accurate studies of molecular interactions and reactions in complex systems.