Reactive Vortexes in a Naturally Activated Process: Non-Diffusive Rotational Fluxes at Transition State Uncovered by Persistent Homology

TL;DR

This study uncovers non-diffusive, vortex-like rotational fluxes in the transition state of alanine-dipeptide isomerization, revealing complex reactive dynamics using topological data analysis.

Contribution

It introduces a novel topological approach to identify reactive vortex regions in natural molecular transition dynamics, challenging the diffusion assumption.

Findings

Identified strong reactive vortex regions in configuration-time space.

Discovered rotational fluxes swirl around transition states multiple times.

Revealed cooperative movement along isocommitter surfaces and orthogonal barrier-crossing.

Abstract

Dynamics of reaction coordinates during barrier-crossing are key to understand activated processes in complex systems such as proteins. The default assumption from Kramers physical intuition is that of a diffusion process. However, the dynamics of barrier-crossing in natural complex molecules are largely unexplored. Here we investigate the transition dynamics of alanine-dipeptide isomerization, the simplest complex system with a large number of non-reaction coordinates that can serve as an adequate thermal bath feeding energy into the reaction coordinates. We separate conformations along the time axis and construct the dynamic probability surface of reaction. We quantify its topological structure and rotational flux using persistent homology and differential form. Our results uncovered a region with strong reactive vortex in the configuration-time space, where the highest probability peak and the transition state ensemble are located. This reactive region contains strong rotational fluxes: Most reactive trajectories swirl multiple times around this region in the subspace of the two most-important reaction coordinates. Furthermore, the rotational fluxes result from cooperative movement along the isocommitter surfaces and orthogonal barrier-crossing. Overall, our findings offer a first glimpse into the reactive vortex regions that characterize the non-diffusive dynamics of barrier-crossing of a naturally occurring activation process.