Cost-Effective Method for Free-Energy Minimization in Complex Systems with Elaborated Ab Initio Potentials.

Area of Science:

• Computational Chemistry
• Theoretical Chemistry
• Molecular Dynamics

Background:

• Accurate determination of molecular system properties requires high-level quantum mechanical calculations.
• Locating stationary points on free-energy hypersurfaces is crucial for understanding chemical reaction mechanisms and kinetics.
• Existing methods can be computationally expensive, limiting their application to complex systems.

Purpose of the Study:

• To develop an efficient computational method for locating stationary points in the free-energy hypersurface of complex molecular systems.
• To enable the use of high-level correlated ab initio potentials in such calculations.
• To reduce computational cost and time for accurate molecular simulations.

Main Methods:

• A dual-level strategy combining QM/MM (Quantum Mechanics/Molecular Mechanics) description.
• Calculation of the free-energy gradient (FEG) as the mean force on nuclei.
• Utilizing statistical simulations with a low-level force field and Free-Energy Perturbation (FEP) theory for high-level derivatives.
• Application to water molecule structure in liquid water using specific ab initio levels of theory.

Main Results:

• The composite FEG-FEP approach accurately reproduces results from standard free-energy minimization.
• Significant reduction in computational and wall-clock time is achieved.
• Geometrical parameters and dipole moment of water in liquid water are calculated with high accuracy, within experimental error.
• Excellent agreement with other theoretical estimations was observed.

Conclusions:

• The developed FEG-FEP methodology offers an efficient and accurate way to study molecular systems using high-level ab initio potentials.
• This advancement facilitates the accurate determination of mechanisms, kinetics, and thermodynamic properties in various chemical environments.
• The method is a significant step towards understanding complex processes in solution, enzymes, and disordered systems.