A Rigorous Method for Identifying a One-Dimensional Reaction Coordinate in Complex Molecules.

Abstract

Understanding the mechanism of functional protein dynamics is critical to understanding protein functions. Reaction coordinate (RC) is a central topic in protein dynamics, and the grail is to find the one-dimensional RC (1D-RC) that can fully determine the value of a committor (i.e., the reaction probability in configuration space) for any protein configuration. We present a new method that, for the first time, uses a fundamental mechanical operator, the generalized work functional, to identify the rigorous 1D-RC in complex molecules. For a prototypical biomolecular isomerization reaction, the 1D-RC identified by the current method can determine the committor with an accuracy far exceeding what was achieved by previous methods. This method only requires modest computational cost and can be readily applied to large molecules. Most importantly, the generalized work functional is the physical determinant of the collectivity in functional protein dynamics and provides a tentative roadmap that connects the structure of a protein to its function.