Assessment of Density Functionals for Intramolecular Dispersion-Rich Interactions

Area of Science:

• Computational Chemistry
• Quantum Chemistry
• Molecular Modeling

Background:

• Accurately describing molecular conformations is crucial in computational chemistry.
• Previous studies highlighted the sensitivity of Tyr-Gly conformer profiles to intramolecular dispersion and basis set superposition error.
• Standard methods like MP2 with small basis sets are inadequate for this system.

Purpose of the Study:

• To assess various density functional theory (DFT) methods for describing the ϕGly rotational profile of a Tyr-Gly conformer.
• To compare the performance of different DFT functionals against a high-level reference (CCSD(T)/CBS).
• To identify the most reliable DFT method for this specific conformational analysis.

Main Methods:

• Evaluation of multiple DFT functionals: hybrid, meta-hybrid, double-hybrid, and DFT-D.
• Calculation of energy profiles for the ϕGly torsion angle variation.
• Comparison of DFT results with an estimated coupled cluster singles and doubles with perturbative triples (CCSD(T))/complete basis set (CBS) reference.

Main Results:

• Hybrid and PWB6K functionals failed to identify all three energy minima.
• M05-2X, M06-2X, M06-L, mPW2-PLYP, and B3LYP-D identified all minima but underestimated relative C-terminus rotated stability.
• The mPW2-PLYP-D method demonstrated the best performance, accurately predicting all minima and their stability order, along with M06-2X.

Conclusions:

• The accuracy of DFT methods in describing conformational energy profiles varies significantly.
• Advanced DFT functionals, particularly double-hybrid functionals with dispersion corrections, are essential for reliable conformational analysis.
• mPW2-PLYP-D and M06-2X are recommended for accurately modeling the Tyr-Gly ϕGly rotational profile.