Stochastic diffusion framework determines the free-energy landscape and rate from single-molecule trajectory

J Chem Phys. 2018 Dec 21;149(23):234107. doi: 10.1063/1.5052142.

Abstract

A theoretical stochastic diffusion framework is developed that characterizes the position-dependent diffusion coefficient [D(Q)] and drift velocity [ v (Q)] by analysing single-molecule time traces [Q(t)]. The free-energy landscape [F(Q)] that governs the dynamics is reconstructed with the calculated D and v . There are many computational tools that perform this task in which some are computationaly demanding, difficult to run, and, most of the time, not directly available to the community. This is a first attempt to implement the simplified stochastic diffusion framework that is fast, easy to run in a Python environment, and available to be extended as needed. It does not require adjustable parameters, inference methods, or sampling bias such as Monte Carlo Bayesian estimators or umbrella samplings. The stochastic framework was applied in the protein-like lattice model with Monte Carlo simulations, which accurately predicted the folding rates with the coordinate-dependent D and F plugged into Kramers' theory. The results were compared with two other independently developed methodologies (the Bayesian analysis and fep1D algorithm) presenting a good match, which confirms its validity. This theoretical framework might be useful in determining the free-energy and rates by providing time series only from biological or condensed-phase systems. The code is freely available at https://github.com/ronaldolab/stochastic_diffusion.

MeSH terms

  • Bayes Theorem
  • Diffusion
  • Hydrophobic and Hydrophilic Interactions
  • Models, Molecular*
  • Molecular Conformation
  • Monte Carlo Method
  • Stochastic Processes
  • Thermodynamics