堆叠和双价介导的静电相互作用之间的竞争决定了短DNA序列的形状
Balaka Mondal1, Debayan Chakraborty1, Naoto Hori2
1Department of Chemistry, The University of Texas, Austin, Texas 78712, United States.
Journal of chemical theory and computation
|March 18, 2024
概括
一个新的计算模型,TIS-ION,准确地模拟了离子-DNA相互作用,揭示了Mg2+和Ca2+的结合偏好. 这促进了对DNA结构和动态的理解,这对核酸稳定性至关重要.
科学领域:
- 计算生物物理学的计算生物物理.
- 对DNA-蛋白相互作用的分子建模.
背景情况:
- 二元子 (Mg2+,Ca2+) 和堆叠相互作用对于DNA稳定性和相分离至关重要.
- 需要定量模型来理解核酸中的离子-DNA相互作用.
- 现有的方法可能会掩盖特定的离子行为.
研究的目的:
- 开发一个依赖序列的计算模型 (TIS-ION) 来模拟离子-DNA相互作用.
- 量化比较模型预测与实验性离子计数和散射数据.
- 阐明Mg2+和Ca2+对DNA的独特结合偏好.
主要方法:
- 开发TIS-ION计算模型,其中包含单价离子和双价离子.
- 对双链DNA (dsDNA) 和单链DNA (ssDNA) 序列的模拟 (dA30,dT30).
- 计算离子过量数,小角度X射线散射 (SAXS) 配置文件,并分析离子结合点.
主要成果:
- TIS-ION模型准确地预测了DNA周围的离子数,与实验性离子计数数据相匹配.
- 从全原子结构中计算的SAXS概况与实验结果很好地一致.
- 2+与小沟和酸盐结合,而Ca2+则表现出特定的小沟结合;两者都喜欢小沟而不是大沟.
结论:
- 该TIS-ION模型提供了对离子-DNA相互作用的定量见解,对实验进行验证.
- 确定了Mg2+和Ca2+与DNA小沟的明显结合行为.
- 该模型的成功为研究涉及离子效应的DNA生物物理学问题开辟了道路.
更多相关视频
09:17Structure-Based Simulation and Sampling of Transcription Factor Protein Movements along DNA from Atomic-Scale Stepping to Coarse-Grained Diffusion
Published on: March 1, 2022
3.1K
09:26DNA-Tethered RNA Polymerase for Programmable In vitro Transcription and Molecular Computation
Published on: December 29, 2021
4.2K
相关概念视频
Single-Strand DNA Binding Proteins
14.1K
For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
14.1K
DNA as a Genetic Template
21.9K
Two structural features of the DNA molecule provide a basis for the mechanisms of heredity: the four nucleotide bases and its double-stranded nature. The Watson-Crick model of double-helical DNA structure, proposed in 1952, drew heavily upon the X-ray crystallography work of researchers Rosalind Franklin and Maurice Wilkins. Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine for their work in 1962. Franklin was, controversially, excluded from the prize for...
21.9K
The Nucleosome
1.5K
Human DNA is almost two meters long. However, it is compressed inside a tiny nucleus measuring only a few microns in diameter. To make this degree of compaction possible, DNA is organized into several sequential levels so that it can fit into such a tiny space. The most compact form of DNA is a chromosome that can be seen under a microscope in a dividing cell.
In a chromosome, DNA is wound twice around a protein complex called a histone octamer core, which consists of 8 histone proteins. This...
In a chromosome, DNA is wound twice around a protein complex called a histone octamer core, which consists of 8 histone proteins. This...
1.5K
Cooperative Binding of Transcription Regulators
6.4K
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
6.4K
Chromatin Packaging
16.7K
Each human somatic cell contains 6 billion base pairs of DNA. Each base pair is 0.34 nm long, meaning each diploid cell contains a staggering 2 meters of DNA. This long DNA strand is packed inside a nucleus measuring only 10-20 microns in diameter with the help of specialized DNA-binding proteins called histones. Together they form a compact DNA-protein complex called chromatin. The chromatin is further compacted into higher-order structures. The highest level of compaction is achieved during...
16.7K
Conserved Binding Sites
4.2K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.2K
