# Investigation of rare protein conformational transitions via dissipation-corrected targeted molecular dynamics

Source: [Investigation of rare protein conformational transitions via dissipation-corrected targeted molecular dynamics](<https://www.sota2.com/research/paper/68fa453e1e209131ce916f00>)

Collection index: [llms.txt](<https://www.sota2.com/research/llms.txt>)

Data updated: 2025-10-25T05:12:10.318Z

Authors: Matthias Post, Steffen Wolf, Gerhard Stock

Published: 2023-09-15T20:57:45.000Z

## Abstract

To sample rare events, dissipation-corrected targeted molecular dynamics (dcTMD) applies a constant velocity constraint along a one-dimensional reaction coordinate $s$, which drives an atomistic system from an initial state into a target state. Employing a cumulant approximation of Jarzynski's identity, the free energy $\\Delta G (s)$ is calculated from the mean external work and dissipated work of the process. By calculating the friction coefficient $\\Gamma (s)$ from the dissipated work, in a second step the equilibrium dynamics of the process can be studied by propagating a Langevin equation. While so far dcTMD has been mostly applied to study the unbinding of protein-ligand complexes, here its applicability to rare conformational transitions within a protein and the prediction of their kinetics is investigated. As this typically requires the introduction of multiple collective variables $\\{x\_j\\}= \\vec{x}$, a theoretical framework is outlined to calculate the associated free energy $\\Delta G (\\vec{x})$ and friction $\\matrix{\\Gamma}(\\vec{x})$ from dcTMD simulations along coordinate $s$. Adopting the $\\alpha$-$\\beta$ transition of alanine dipeptide as well as the open-closed transition of T4 lysozyme as representative examples, the virtues and shortcomings of dcTMD to predict protein conformational transitions and the related kinetics are studied.

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## Original sources and implementation

[Original paper](<https://arxiv.org/abs/2309.08759>)

[PDF](<https://arxiv.org/pdf/2309.08759.pdf>)