How fluxional reactants limit the accuracy/efficiency of infrequent metadynamics

Area of Science:

• Computational Chemistry
• Molecular Dynamics
• Reaction Rate Theory

Background:

• Infrequent metadynamics (iMetaD) is a computational method for estimating unbiased reaction rates.
• iMetaD utilizes a bias potential in collective variable (CV) space, differing from hyperdynamics' configuration space approach.
• Rate estimation accuracy in iMetaD can be sensitive to CV choice and simulation parameters.

Purpose of the Study:

• To investigate the impact of reactant dynamics on iMetaD parameter selection.
• To illustrate potential complications in systems with fluxional reactant states.
• To establish bounds for admissible iMetaD parameters based on system dynamics.

Main Methods:

• Development and analysis of a simplified discrete state model.
• Application of iMetaD simulations to a corresponding 2D potential energy surface.
• Validation of discrete model predictions against iMetaD simulation results.

Main Results:

• The discrete state model demonstrates how reactant-to-product escape times and intra-reactant basin relaxation times constrain iMetaD parameter choices.
• Complications arise in systems with fluxional transitions between reactant sub-basins.
• Parameter choices must account for both escape and relaxation dynamics for accurate rate estimation.

Conclusions:

• Accurate infrequent metadynamics simulations require careful consideration of the interplay between system escape rates and internal relaxation dynamics.
• The choice of collective variables and bias deposition parameters significantly impacts rate estimates.
• Discrete state models can effectively illustrate and predict challenges in advanced molecular simulation techniques.