Maffeo Christopher, Chou Han-Yi, Aksimentiev Aleksei
Department of Physics, University of Illinois at Urbana-Champaign, 1110 W Green St, Urbana, 61801 IL, USA.
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, 405 N Matthews Avenue, Urbana, 61801 IL, USA.
iScience. 2022 Apr 18;25(5):104264. doi: 10.1016/j.isci.2022.104264. eCollection 2022 May 20.
The interpretation of single-molecule experiments is frequently aided by computational modeling of biomolecular dynamics. The growth of computing power and ongoing validation of computational models suggest that it soon may be possible to replace some experiments outright with computational mimics. Here, we offer a blueprint for performing single-molecule studies using a DNA-binding protein as a test bed. We demonstrate how atomistic simulations, typically limited to sub-millisecond durations and zeptoliter volumes, can guide development of a coarse-grained model for use in simulations that mimic single-molecule experiments. We apply the model to recapitulate, , force-extension characterization of protein binding to single-stranded DNA and protein and DNA replacement assays, providing a detailed portrait of the underlying mechanics. Finally, we use the model to simulate the trombone loop of a replication fork, a large complex of proteins and DNA.
单分子实验的解释常常借助于生物分子动力学的计算建模。计算能力的提升以及计算模型的不断验证表明，用计算模拟直接取代某些实验可能很快就能实现。在此，我们提供了一个以DNA结合蛋白为测试平台进行单分子研究的蓝图。我们展示了通常限于亚毫秒时长和zeptoliter体积的原子模拟如何能够指导粗粒度模型的开发，该模型用于模拟单分子实验的模拟。我们应用该模型来重现蛋白质与单链DNA结合的力-伸长特性以及蛋白质和DNA置换实验，提供了潜在力学的详细描述。最后，我们用该模型模拟复制叉的长号环，这是一个由蛋白质和DNA组成的大型复合物。
