从无偏的全原子分子动力学模拟中对与艾滋病毒相关的氨基基PAP248-286的二元化和交叉β片形成的机械洞察力
Nikhil Agrawal1,2, Emilio Parisini1,3
1Latvian Institute of Organic Synthesis, Riga 1006, Latvia.
Computational and structural biotechnology journal
|January 15, 2026
概括
精液衍生的病毒感染增强剂 (SEVI) 纤维素通过聚形成. 分子动力学模拟揭示了驱动SEVI纤维细胞形成的初始步骤的关键相互作用,这对于艾滋病毒传播至关重要.
科学领域:
- 生物物理学的生物物理.
- 分子生物学分子生物学
- 病毒学 病毒学
背景情况:
- 来自精液的病毒感染增强剂 (SEVI) 纤维,由PAP248-286形成,通过帮助病毒附着增强HIV传播.
- 在SEVI核化和早期聚合的基础上存在的分子机制尚不清楚.
研究的目的:
- 阐明PAP248-286二聚化和解离的分子基础.
- 在原子层面上研究SEVI纤维组装的最早步骤.
主要方法:
- 进行了80个独立的全原子分子动力学 (MD) 模拟 (共40μs).
- 执行了100个独立的导向MD和采样运行.
- 分析了相关性,β片形成和间结合相互作用.
主要成果:
- 联结和β叶形成是由合作性键和疏水性相互作用驱动的.
- 关键残留物 (Arg10,Val17,Glu19,Ile20) 极大地促进了际结合,形成了硬质拉链图案.
- 机械弹性二次体表现出多障碍解结行为,解离的自由能量为8.7kcal/mol.
结论:
- 在PAP248-286二元体中的小β片核作为合作中间体.
- 这些二分体播种形成全长的交叉β SEVI纤维.
- 提供了对SEVI纤维细胞组装的初始阶段的原子洞察力,这与艾滋病毒传播有关.
更多相关视频
14:55Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy
Published on: September 17, 2017
15.9K
10:50Assessment of Immunologically Relevant Dynamic Tertiary Structural Features of the HIV-1 V3 Loop Crown R2 Sequence by ab initio Folding
Published on: September 15, 2010
9.9K
相关概念视频
Amyloid Fibrils
11.6K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
11.6K
Protein Folding
11.1K
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
11.1K
Protein Folding
126.3K
Overview
126.3K
Protein Complex Assembly
16.6K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
16.6K
