# A variational conformational dynamics approach to the selection of collective variables in metadynamics

## TL;DR

This paper introduces a novel method combining metadynamics and time-lagged independent component analysis to improve the selection of collective variables, enhancing the study of rare events and complex free energy landscapes.

## Contribution

The paper presents a new variational conformational dynamics approach that optimizes collective variables for metadynamics using conformational analysis techniques.

## Key findings

- More efficient collective variables are obtained.
- Improved convergence in free energy landscape exploration.
- Enhanced understanding of system physics.

## Abstract

In this paper we combine two powerful computational techniques, well-tempered metadynamics and time lagged independent component analysis. The aim is to develop a new tool for studying rare events and exploring complex free energy landscapes. Metadynamics is a well-established and widely used enhanced sampling method whose efficiency depends on an appropriate choice of collective variables. Often the initial choice is not optimal leading to slow convergence. However by analyzing the dynamics generated in one such a run with a time-lagged independent component analysis and the techniques recently developed in the area of conformational dynamics, we obtain much more efficient collective variables, that are also better capable of illuminating the physics of the system. We demonstrate the power of this approach in two paradigmatic examples.