Coupled-perturbed DFTB-QM/MM metadynamics: Application to proton-coupled electron transfer.

Area of Science:

• Computational Chemistry
• Molecular Dynamics Simulations
• Quantum Chemistry

Background:

• Free energy calculations are crucial for understanding chemical reaction mechanisms.
• Existing methods may face challenges in accurately simulating complex processes like proton-coupled electron transfer.
• Advanced simulation techniques are needed to improve the accuracy and efficiency of these calculations.

Purpose of the Study:

• To present a new computational scheme for free energy calculations of chemical reactions.
• To apply and evaluate this method for proton-coupled electron transfer in a model system.
• To identify the strengths and limitations of the proposed methodology.

Main Methods:

• Utilized extended sampling molecular dynamics simulations with biasing potentials on partial atomic charges.
• Combined biasing potentials with atomic coordinates in single or multi-dimensional collective variables.
• Employed the approximative density-functional tight-binding method to obtain necessary gradients.
• Implemented the computational scheme using Gromacs and Plumed software.
• Studied proton-coupled electron transfer using two collective variables for proton and electron transfer.

Main Results:

• The new method correctly identified free energy minima and the mechanism of proton-coupled electron transfer.
• Results showed qualitative agreement with extended free simulations.
• The topology of the transition region and energy barrier height were reproduced qualitatively.
• Identified potential challenges including inefficient spatial sampling and decreased simulation stability.

Conclusions:

• The developed approach offers a viable alternative for free energy calculations in specific chemical reactions, such as proton-coupled electron transfer in proteins.
• The method successfully captures key aspects of reaction mechanisms.
• Further refinement may be needed to address sampling and stability issues for broader applicability.