An implementation of the maximum-caliber principle by replica-averaged time-resolved restrained simulations

TL;DR

This paper demonstrates that replica-averaged molecular simulations with time-dependent restraints can implement the maximum caliber principle, enabling the integration of time-resolved experimental data into molecular dynamics simulations.

Contribution

It establishes the theoretical equivalence between time-dependent restrained simulations and the maximum caliber principle, extending the maximum entropy framework to dynamic data integration.

Findings

Analytical proof of equivalence between time-dependent restraints and maximum caliber

Computational validation using simple models and synthetic data

Discussion of limitations and potential solutions

Abstract

Inferential methods can be used to integrate experimental informations and molecular simulations. The maximum entropy principle provides a framework for using equilibrium experimental data and it has been shown that replica-averaged simulations, restrained using a static potential, are a practical and powerful implementation of such principle. Here we show that replica-averaged simulations restrained using a time-dependent potential are equivalent to the principle of maximum caliber, the dynamic version of the principle of maximum entropy, and thus may allow to integrate time-resolved data in molecular dynamics simulations. We provide an analytical proof of the equivalence as well as a computational validation making use of simple models and synthetic data. Some limitations and possible solutions are also discussed.