Nuclear-Electronic Orbital QM/MM Approach: Geometry Optimizations and Molecular Dynamics.

Area of Science:

• Computational Chemistry
• Quantum Mechanics
• Molecular Mechanics

Background:

• Hybrid quantum mechanical/molecular mechanical (QM/MM) methods are crucial for simulating chemical reactions in complex environments like proteins.
• Accurate modeling requires accounting for quantum mechanical effects of specific nuclei, particularly protons.

Purpose of the Study:

• Introduce the nuclear-electronic orbital (NEO) QM/MM approach for quantizing nuclei, specifically protons, within the QM region.
• Enable detailed simulations of proton delocalization, polarization, anharmonicity, and zero-point energy.
• Provide theoretical framework and initial applications for advanced simulations.

Main Methods:

• Developed the NEO-QM/MM method, integrating NEO-density functional theory (NEO-DFT) with QM/MM.
• Derived expressions for energies and analytical gradients for NEO-QM/MM and NEO-PCM (polarizable continuum model).
• Performed geometry optimizations and real-time direct dynamics simulations.

Main Results:

• Demonstrated that aqueous solvation strengthens hydrogen-bonding interactions, evidenced by shorter intermolecular distances.
• Successfully simulated a phenol molecule in explicit water using NEO-QM/MM.
• Validated the inclusion of proton quantum effects in simulations.

Conclusions:

• The NEO-QM/MM method provides a robust framework for studying nuclear-electronic quantum dynamics.
• This approach is foundational for future investigations in complex chemical and biological systems.
• Highlights the significant impact of solvation on molecular interactions.