Department of Mechanical Engineering and Applied Mechanics , University of Pennsylvania , Philadelphia , Pennsylvania 19104 , United States.
J Phys Chem B. 2019 Jan 10;123(1):21-28. doi: 10.1021/acs.jpcb.8b07501. Epub 2018 Dec 31.
Allosteric interactions in DNA are crucial for various biological processes. These interactions are quantified by measuring the change in free energy as a function of the distance between the binding sites for two ligands. Here, we show that trends in the interaction energy of ligands binding to DNA can be explained within an elastic birod model, which accounts for the deformation of each strand as well as the change in stacking energy due to perturbations in position and orientation of the bases caused by the binding of ligands. The strain fields produced by the ligands decay with distance from the binding site. The interaction energy of two ligands decays exponentially with the distance between them and oscillates with the periodicity of the double helix in quantitative agreement with experimental measurements. The trend in the computed interaction energy is similar to that in the perturbation of groove width produced by the binding of a single ligand, which is consistent with molecular simulations. Our analysis provides a new framework to understand allosteric interactions in DNA and can be extended to other rod-like macromolecules whose elasticity plays a role in biological functions.
变构相互作用在 DNA 中对于各种生物学过程至关重要。这些相互作用通过测量两个配体结合位点之间的距离作为自由能变化的函数来定量。在这里,我们表明,结合到 DNA 的配体的相互作用能趋势可以用弹性双螺旋模型来解释,该模型考虑了每个链的变形以及由于配体结合引起的碱基位置和取向的扰动导致的堆积能的变化。配体产生的应变场随距结合位点的距离而衰减。两个配体之间的相互作用能随它们之间的距离呈指数衰减,并与实验测量的双螺旋周期性呈振荡关系,定量一致。计算出的相互作用能趋势与单个配体结合产生的沟宽扰动的趋势相似,这与分子模拟一致。我们的分析为理解 DNA 中的变构相互作用提供了一个新的框架,并且可以扩展到其他在生物学功能中发挥作用的棒状大分子。