Okazaki Kei-Ichi, Nakamura Akihiko, Iino Ryota
Department of Theoretical and Computational Molecular Science, Institute for Molecular Science, National Institutes of Natural Sciences, Okazaki, 444-8585, Japan.
Department of Life and Coordination-Complex Molecular Science, Institute for Molecular Science, National Institutes of Natural Sciences, Okazaki, 444-8787, Japan.
J Phys Chem B. 2020 Jul 30;124(30):6475-6487. doi: 10.1021/acs.jpcb.0c02698. Epub 2020 Jul 20.
The mechanism of biomolecular motors has been elucidated using single-molecule experiments for visualizing motor motion. However, it remains elusive that how changes in the chemical state during the catalytic cycle of motors lead to unidirectional motions. In this study, we use single-molecule trajectories to estimate an underlying diffusion model with chemical-state-dependent free energy profile. To consider nonequilibrium trajectories driven by the chemical energy consumed by biomolecular motors, we develop a novel framework based on a hidden Markov model, wherein switching among multiple energy profiles occurs reflecting the chemical state changes in motors. The method is tested using simulation trajectories and applied to single-molecule trajectories of processive chitinase, a linear motor that is driven by the hydrolysis energy of a single chitin chain. The chemical-state-dependent free energy profile underlying the burnt-bridge Brownian ratchet mechanism of processive chitinase is determined. The novel framework allows us to connect the chemical state changes to the unidirectional motion of biomolecular motors.
通过用于可视化分子马达运动的单分子实验，生物分子马达的机制已得到阐明。然而，马达催化循环过程中化学状态的变化如何导致单向运动，这一点仍然不清楚。在本研究中，我们使用单分子轨迹来估计具有化学状态依赖自由能分布的潜在扩散模型。为了考虑由生物分子马达消耗的化学能驱动的非平衡轨迹，我们基于隐马尔可夫模型开发了一个新框架，其中多个能量分布之间的切换反映了马达中的化学状态变化。该方法通过模拟轨迹进行测试，并应用于持续性几丁质酶的单分子轨迹，持续性几丁质酶是一种由单个几丁质链的水解能量驱动的线性马达。确定了持续性几丁质酶的烧桥布朗棘轮机制背后的化学状态依赖自由能分布。这个新框架使我们能够将化学状态变化与生物分子马达的单向运动联系起来。
