What tunes guanine ionization potential in a nucleosome? An all-in-one systematic QM/MM assessment.

IF 3.2 3区生物学 Q2 BIOPHYSICS

Biophysical journal Pub Date : 2024-09-17 Epub Date: 2024-07-10 DOI:10.1016/j.bpj.2024.07.009

Maxime Kermarrec, Elise Dumont, Natacha Gillet

引用次数: 0

Abstract

Guanine radical cations are precursors to oxidatively induced DNA lesions, and the determination of oxidative DNA hot spots beyond oligonucleotides remains a current challenge. In order to rationalize the finetuned ionization properties of the ∼60 guanines in a nucleosome core particle, we report a robust molecular dynamics-then-FO-DFTB/MM (fragment-orbital tight-binding density functional theory/molecular mechanics) simulation protocol spanning 20 μs. Our work allows us to identify several factors governing guanine ionization potential and map oxidative hotspots. Our results highlight the predominant role of the proximity of positively charged histone residues in the modulation of the guanine ionization potential up to 0.6 eV. Consequently, fast, long-range hole transfer in nucleosomal DNA could be tuned by the proximity of histone tails, which differs, from a biological point of view, on the chromatin state.

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核小体中的鸟嘌呤电离电位如何调节？QM/MM 一体化系统评估。

鸟嘌呤自由基阳离子是氧化诱导 DNA 病变的前体，确定寡核苷酸以外的 DNA 氧化热点仍然是当前的一项挑战。为了合理解释核糖体核心颗粒（NCP）中 60 个鸟嘌呤的微调电离特性，我们报告了一个强大的 MD-then-FO-DFTB/MM 模拟方案，时间跨度为 20 微秒。我们的工作有助于确定鸟嘌呤电离电位的几个影响因素，并绘制氧化热点图。我们的研究结果表明，带正电荷的组蛋白残基在鸟嘌呤电离电位的调节（最高可达 0.6 eV）中起着主导作用。因此，核糖体 DNA 中的快速远距离空穴传输可能因组蛋白尾部的邻近程度而异，因此从生物学角度来看，也可能因染色质状态而异。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biophysical journal 生物-生物物理

CiteScore

6.10

自引率

5.90%

发文量

3090

审稿时长

2 months

期刊介绍： BJ publishes original articles, letters, and perspectives on important problems in modern biophysics. The papers should be written so as to be of interest to a broad community of biophysicists. BJ welcomes experimental studies that employ quantitative physical approaches for the study of biological systems, including or spanning scales from molecule to whole organism. Experimental studies of a purely descriptive or phenomenological nature, with no theoretical or mechanistic underpinning, are not appropriate for publication in BJ. Theoretical studies should offer new insights into the understanding ofexperimental results or suggest new experimentally testable hypotheses. Articles reporting significant methodological or technological advances, which have potential to open new areas of biophysical investigation, are also suitable for publication in BJ. Papers describing improvements in accuracy or speed of existing methods or extra detail within methods described previously are not suitable for BJ.