Non-covalent Interactions at the QM-MM Interface in the Semiempirical and Density Functional Limit

Area of Science:

• Computational chemistry
• Molecular modeling
• Biophysics

Background:

• Non-covalent interactions are crucial in chemical and biological systems.
• Quantum mechanics/molecular mechanics (QM/MM) methods offer a hybrid approach to model these interactions.
• Understanding QM/MM limitations is vital for accurate simulations.

Purpose of the Study:

• To evaluate the accuracy of QM/MM methods for hydrogen-bonded complexes.
• To identify the impact of the QM-MM boundary on non-covalent interaction calculations.
• To provide guidelines for optimal QM/MM model setup.

Main Methods:

• Utilized density functional theory (DFT) and density functional tight binding (DFTB) for the QM region.
• Employed the general Amber force field (GAFF) for the molecular mechanics (MM) region.
• Investigated neutral and ionic dimers, as well as cluster-type microenvironments.

Main Results:

• The QM-MM interface significantly contributes to errors, even with advanced QM methods.
• For neutral dimers, GAFF/ωB97X-V provided the most accurate results, with errors linked to polarity and polarizability.
• Ionic dimers require the QM region to include charge transfer and hydrogen bonds to avoid sharp error increases.
• Short intermolecular distances and unoptimized LJ parameters also led to poor QM/MM performance.
• QM/MM models showed lower relative errors in cluster environments compared to gas-phase dimers.

Conclusions:

• Careful selection of the QM region, including hydrogen-bond acceptors and charge transfer regions, is critical for QM/MM accuracy.
• Avoiding QM-MM boundaries across ionic hydrogen bonds is essential.
• QM/MM topologies for AMBER and GROMACS are provided to facilitate further research.