Reaction Coordinates are Optimal Channels of Energy Flow

TL;DR

This paper reviews 25 years of progress in identifying reaction coordinates in proteins, emphasizing physics-based methods that reveal these coordinates as optimal energy flow channels crucial for understanding protein function.

Contribution

It introduces a rigorous energy flow theory and generalized work functional method for objectively identifying true reaction coordinates in biomolecules.

Findings

Energy flow theory reveals RCs as optimal energy channels

Generalized work functional method provides a rigorous identification approach

RCs are essential for understanding protein conformational changes

Abstract

Reaction coordinates (RCs) are the few essential coordinates of a protein that control its functional processes, such as allostery, enzymatic reaction, and conformational change. They are critical for understanding protein function and provide optimal enhanced sampling of protein conformational changes and states. Since the pioneering works in the late 1990s, identifying the correct and objectively provable RCs has been a central topic in molecular biophysics and chemical physics. This review summarizes the major advances in identifying RCs over the past 25 years, focusing on methods aimed at finding RCs that meet the rigorous committor criterion, widely accepted as the true RCs. Importantly, the newly developed physics-based energy flow theory and generalized work functional method provide a general and rigorous approach for identifying true RCs, revealing their physical nature as the optimal channels of energy flow in biomolecules.