Maximum Flux Transition Paths of Conformational Change

TL;DR

This paper introduces a novel method for identifying the most probable transition paths between metastable states in biomolecular systems using maximum flux paths based on committor functions, improving path accuracy.

Contribution

It proposes a new maximum flux transition path method that differs from previous approaches, employing a robust algorithm to solve a boundary-value problem for transition path calculation.

Findings

The maximum flux path is closer to an ideal transition path than previous methods.

A simple, robust algorithm for computing the path is developed.

The method effectively approximates transition paths in biomolecular systems.

Abstract

Given two metastable states A and B of a biomolecular system, the problem is to calculate the likely paths of the transition from A to B. Such a calculation is more informative and more manageable if done for a reduced set of collective variables chosen so that paths cluster in collective variable space. The computational task becomes that of computing the "center" of such a cluster. A good way to define the center employs the concept of a committor, whose value at a point in collective variable space is the probability that a trajectory at that point will reach B before A. The committor "foliates" the transition region into a set of isocommittors. The maximum flux transition path is defined as a path that crosses each isocommittor at a point which (locally) has the highest crossing rate of distinct reactive trajectories. (This path is different from that of the MaxFlux method of Huo and Straub.) It is argued that such a path is nearer to an ideal path than others that have been proposed with the possible exception of the finite-temperature string method path. To make the calculation tractable, three approximations are introduced, yielding a path that is the solution of a nonsingular two-point boundary-value problem. For such a problem, one can construct a simple and robust algorithm. One such algorithm and its performance is discussed.