Afanasyev Alexander Y, Onufriev Alexey V
Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
Departments of Computer Science and Physics, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
bioRxiv. 2025 Feb 28:2023.03.12.532320. doi: 10.1101/2023.03.12.532320.
When highly stretched, double-stranded DNA exhibits a plateau region in its force-extension curve. Using a bead-spring coarse-grained dynamic model based on a non-convex potential, we predict that a long double-stranded DNA fragment made of several consecutive segments with substantially different plateau force values for each segment will exhibit multiple distinct plateau regions in the force-extension curve under physiologically relevant solvent conditions. For example, a long composite double-stranded (ds) DNA fragment consisting of two equal-length segments characterized by two different plateau force values, such as the poly(dA-dT)-poly(dG-dC) fragment, is predicted to exhibit two distinct plateau regions in its force-extension curve; a long composite dsDNA fragment consisting of three segments having three different plateau force values is predicted to have three distinct plateau regions. The formation of mixed states of slightly and highly stretched DNA, co-existing with macroscopically distinct phases of uniformly stretched DNA is also predicted. When one of the segments overstretches, the extensions of the segments can differ drastically. For example, for the poly(dA-dT)-poly(dG-dC) composite fragment, in the middle of the first plateau, 96.7 % of the total extension of the fragment (relative to ) comes from the poly(dA-dT) segment, while only 3.3 % of it comes from the poly(dG-dC) segment. The order of the segments has little effect on the force-extension curve or the distribution of conformational states. We speculate that the distinct structural states of stretched double-stranded DNA may have functional importance. For example, these states may modulate, in a sequence-dependent manner, the rate of double-stranded DNA processing by key cellular machines.
当双链DNA受到高度拉伸时，其力 - 伸长曲线会出现一个平台区域。我们使用基于非凸势的珠簧粗粒化动力学模型预测，由几个连续片段组成的长双链DNA片段，每个片段具有显著不同的平台力值，在生理相关的溶剂条件下，其力 - 伸长曲线将呈现多个不同的平台区域。例如，由两个等长片段组成的长复合双链（ds）DNA片段，其特征在于两个不同的平台力值，如聚（dA - dT）-聚（dG - dC）片段，预计在其力 - 伸长曲线中会呈现两个不同的平台区域；由三个具有三个不同平台力值的片段组成的长复合dsDNA片段预计会有三个不同的平台区域。还预测了轻微拉伸和高度拉伸的DNA混合状态的形成，与均匀拉伸的DNA宏观上不同的相共存。当其中一个片段过度拉伸时，各片段的伸长可能会有很大差异。例如，对于聚（dA - dT）-聚（dG - dC）复合片段，在第一个平台的中间，片段总伸长的96.7%（相对于 ）来自聚（dA - dT）片段而只有3.3%来自聚（dG - dC）片段。片段的顺序对力 - 伸长曲线或构象状态的分布影响很小。我们推测拉伸的双链DNA的不同结构状态可能具有功能重要性。例如，这些状态可能以序列依赖的方式调节关键细胞机器对双链DNA的加工速率。
