Transition path times in asymmetric barriers.

Area of Science:

• Biophysics
• Chemical Physics
• Computational Biology

Background:

• Biomolecular conformational transitions are often modeled as barrier crossings in free energy landscapes.
• Transition path times (TPT) quantify the duration of these crossing events.
• The standard model uses a symmetric parabolic barrier, but empirical data sometimes shows discrepancies.

Purpose of the Study:

• To investigate transition path times (TPT) for free energy landscapes with barriers deviating from the symmetric parabolic shape.
• To understand how barrier asymmetry affects the estimation of kinetic parameters.
• To reconcile disagreements between TPT-derived barrier heights and those from other analyses.

Main Methods:

• Introduction of a continuous set of potentials, allowing tunable asymmetry from a parabolic base.
• Analysis of transition path time distributions for these asymmetric potentials.
• Comparison of TPT distributions from asymmetric barriers with fits from symmetric parabolic models.
• Eigenvalue spectrum analysis of the Fokker-Planck equation.

Main Results:

• TPT distributions from asymmetric barriers are well-fitted by symmetric parabolic barrier models.
• However, these fits yield inaccurate barrier heights and diffusion coefficients compared to input values.
• The deviations can be explained by analyzing the Fokker-Planck equation's eigenvalue spectrum.

Conclusions:

• Simple parabolic barrier models can lead to significant errors when applied to asymmetric free energy landscapes.
• Accurate modeling of biomolecular transitions requires accounting for barrier asymmetry.
• The findings offer insights into experimental data interpretation and suggest refinements for kinetic analysis.