Difficulties in applying pure Kohn-Sham density functional theory electronic structure methods to protein molecules

Area of Science:

• Computational Chemistry
• Quantum Chemistry
• Biomolecular Modeling

Background:

• Kohn-Sham Density Functional Theory (KS-DFT) is a powerful method for electronic structure calculations.
• Protein-like molecules and polyproline helices present challenges for standard KS-DFT due to convergence issues.
• The HOMO-LUMO gap is a critical factor influencing the convergence of KS-DFT calculations.

Purpose of the Study:

• To investigate the convergence of KS-DFT electronic structure calculations for protein-like molecules.
• To explore the impact of different density functionals and solvent models on calculation convergence.
• To identify strategies for achieving reliable electronic structure results for biomolecular systems.

Main Methods:

• Utilized Gaussian basis sets for KS-DFT calculations on 17 protein-like molecules and polyproline I helix sequences.
• Tested pure functionals (BLYP, PBE, LDA) and hybrid functionals (BHandHLYP, B3LYP, PBE0), including Hartree-Fock.
• Investigated the effect of explicit solvent molecules and a simplified point charge model for solvent representation.

Main Results:

• Many KS-DFT calculations failed to converge due to vanishing HOMO-LUMO gaps, particularly with pure functionals for longer polyproline helices.
• Including explicit solvent molecules improved the HOMO-LUMO gap but did not fully resolve convergence issues with pure functionals.
• Representing solvent water molecules with a point charge distribution successfully yielded non-vanishing HOMO-LUMO gaps, enabling convergence for pure functionals.

Conclusions:

• Standard KS-DFT calculations face convergence challenges for protein-like systems, often linked to small HOMO-LUMO gaps.
• Hybrid functionals and appropriate solvent modeling are crucial for obtaining converged electronic structure results.
• A point charge model for solvent offers a practical approach to overcome convergence issues in pure functional KS-DFT calculations for biomolecular systems.