Analysis of transition rates from variational flooding using analytical theory

Area of Science:

• Computational chemistry
• Statistical mechanics

Background:

• Enhanced sampling methods accelerate rare events in molecular dynamics.
• Conformational flooding uses boost potentials along reaction coordinates.
• Kramers' theory models barrier crossing dynamics.

Purpose of the Study:

• To model the distribution of crossing times from variational flooding simulations using analytical Kramers' time-dependent rate (KTR) theory.
• To extract unbiased kinetic rates by fitting simulation data to KTR theory.
• To develop an optimized bias potential for enhanced sampling.

Main Methods:

• Constructing an optimized bias potential using the variationally enhanced sampling (VES) method.
• Augmenting the VES-derived potential with a switching function for boost level control.
• Applying analytical KTR theory to model crossing time distributions.
• Utilizing both static and time-dependent boost potentials.

Main Results:

• The empirical distribution of crossing times from variational flooding simulations can be accurately modeled by KTR theory.
• A time-dependent boost potential simplifies the fitting procedure for extracting unbiased rates.
• Static boost potentials yield exponential crossing time distributions, allowing rate extraction at discrete fill levels.
• The method was successfully demonstrated on alanine dipeptide, an SN2 reaction, and chignolin folding.

Conclusions:

• Variational flooding combined with KTR theory provides a robust framework for calculating kinetic rates.
• Time-dependent boost potentials offer a more streamlined approach for rate determination.
• The demonstrated applications highlight the versatility of the method in complex molecular systems.