Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, United States.
Departments of Computer Science and Physics, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, United States.
J Chem Theory Comput. 2022 Jun 14;18(6):3911-3920. doi: 10.1021/acs.jctc.1c01221. Epub 2022 May 11.
We propose an approach to help interpret polymer force-extension curves that exhibit plateau regimes. When coupled to a bead-spring dynamic model, the approach accurately reproduces a variety of experimental force-extension curves of long double-stranded DNA and RNA, including torsionally constrained and unconstrained DNA and negatively supercoiled DNA. A key feature of the model is a specific nonconvex energy function of the spring. We provide an algorithm to obtain the five required parameters of the model from experimental force-extension curves. The applicability of the approach to the force-extension curves of double-stranded (ds) DNA of variable GC content as well as to a DNA/RNA hybrid structure is explored and confirmed. We use the approach to explain counterintuitive sequence-dependent trends and make predictions. In the plateau region of the force-extension curves, our molecular dynamics simulations show that the polymer separates into a mix of weakly and strongly stretched states without forming macroscopically distinct phases. The distribution of these states is predicted to depend on the sequence.
我们提出了一种方法来帮助解释呈现平台区的聚合物力-伸长曲线。当与珠子-弹簧动态模型结合时,该方法能够准确地再现多种长双链 DNA 和 RNA 的实验力-伸长曲线,包括扭转约束和无约束的 DNA 以及负超螺旋 DNA。该模型的一个关键特征是弹簧的特定非凸能量函数。我们提供了一种从实验力-伸长曲线中获得模型所需的五个参数的算法。该方法适用于不同 GC 含量的双链 (ds) DNA 的力-伸长曲线以及 DNA/RNA 杂交结构,并得到了验证。我们使用该方法来解释违反直觉的序列依赖性趋势并进行预测。在力-伸长曲线的平台区,我们的分子动力学模拟表明,聚合物分离成弱拉伸和强拉伸状态的混合物,而不会形成宏观上不同的相。这些状态的分布预计取决于序列。