We propose a methodology for the study of protein-DNA electrostatic interactions and apply it to clarify the effect of histone tails in nucleosomes. This method can be used to correlate electrostatic interactions to structural and functional features of protein-DNA systems, and can be combined with coarse-grained representations. In particular, we focus on the electrostatic field and resulting forces acting on the DNA. We investigate the electrostatic origins of effects such as different stages in DNA unwrapping, nucleosome destabilization upon histone tail truncation, and the role of specific arginines and lysines undergoing Post-Translational Modifications. We find that the positioning of the histone tails can oppose the attractive pull of the histone core, locally deform the DNA, and tune DNA unwrapping. Small conformational variations in the often overlooked H2A C-terminal tails had significant electrostatic repercussions near the DNA entry and exit sites. The H2A N-terminal tail exerts attractive electrostatic forces towards the histone core in positions where Polymerase II halts its progress. We validate our results with comparisons to previous experimental and computational observations.

我们提出了一种研究蛋白质-DNA静电相互作用的方法，并将其应用于阐明组蛋白尾部在核小体中的作用。该方法可用于使静电相互作用与蛋白质-DNA系统的结构和功能特征相关联，并可与粗粒度表示形式结合使用。特别是，我们专注于静电场以及作用在DNA上的合力。我们研究了静电的起源，如DNA解缠的不同阶段，组蛋白尾巴截断时核小体失稳以及特定精氨酸和赖氨酸在翻译后修饰中的作用等。我们发现，组蛋白尾巴的定位可以对抗组蛋白核心的吸引力，使DNA局部变形，并调节DNA的解缠。在经常被忽视的H2A C末端尾巴中的小构象变化在DNA入口和出口位点附近具有明显的静电影响。H2A N末端的尾巴在聚合酶II阻止其进展的位置向组蛋白核心施加有吸引力的静电力。我们通过与以前的实验和计算观察结果进行比较来验证我们的结果。