二硫化物介导对人类酸的形状动态的结构和能量效应
Fengjuan Huang1, Ying Zhang1, Xiaohan Zhang2
1Ningbo Institute of Innovation for Combined Medicine and Engineering, the Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, 315211, China.
International journal of biological macromolecules
|December 25, 2025
概括
人类素 (hCT) 聚合,骨疾病治疗的挑战,通过模拟来澄清. C1-C7二硫化键对hCT结构和聚合至关重要,为设计改进的治疗类型提供了洞察力.
科学领域:
- 生物化学 生物化学
- 计算生物学 计算生物学
- 结构生物学 结构生物学
背景情况:
- 人类素 (hCT) 调节平衡,但聚合成粉样结构,限制其治疗骨疾病的使用.
- 对于hCT聚合的分子基础,特别是C1-C7二硫化键的作用,尚不清楚.
研究的目的:
- 通过分子动力学模拟,在氧化和还原条件下研究hCT的结构动力学和聚合机制.
- 阐明C1-C7二硫化键在hCT折叠,结构稳定性和自我组装中的特定作用.
主要方法:
- 对氧化 (hCTSS) 和减少 (hCTSH) 人类素进行了广泛的原子离散分子动力学 (DMD) 模拟.
- 对单体和自组装状态进行了分析,分析了 conformational 动态,聚合路径和自由能量景观.
主要成果:
- 单体hCTSS和hCTSH存在于具有过渡螺旋的无序结构中;二硫化键裂解促进了N端螺旋到β片的过渡.
- 这两种形式都聚合成由残留物17-22稳定的富含β片的结构;二硫化物裂变增强了β毛形成 (残留物3-13).
- 自由能量分析表明,无序的状态是以态稳定,而β-sheet聚合物则是以态稳定.
结论:
- C1-C7二硫化键显著影响hCT的结构动态和聚合倾向.
- 二硫化物键裂解促进了特定的结构转变和聚合途径.
- 这些发现为设计增强治疗应用的聚合耐药hCT类似物提供了分子洞察力.
更多相关视频
09:15Measuring Biomolecular DSC Profiles with Thermolabile Ligands to Rapidly Characterize Folding and Binding Interactions
Published on: November 21, 2017
8.7K
19:16The Importance of Correct Protein Concentration for Kinetics and Affinity Determination in Structure-function Analysis
Published on: March 17, 2010
21.0K
相关概念视频
Synthesis and Functions of Calcitonin
4.0K
Calcitonin, a vital polypeptide hormone, regulates calcium levels within body fluids. It is released by the parafollicular cells, also known as C cells, situated in the follicular epithelium of the thyroid gland. Calcitonin responds to fluctuations in blood calcium levels and the influence of gastrointestinal hormones like gastrin and cholecystokinin.
The exact mechanisms by which calcitonin operates in calcium homeostasis remain elusive, but its significance is evident in several vital...
The exact mechanisms by which calcitonin operates in calcium homeostasis remain elusive, but its significance is evident in several vital...
4.0K
Protein Folding
10.9K
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...
10.9K
Protein Folding
125.7K
Overview
125.7K
Protein and Protein Structure
86.6K
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme...
A protein's shape is critical to its function. For example, an enzyme...
86.6K
Hormones and Bone Tissue
3.6K
The endocrine system produces and secretes hormones, which interact with the skeletal system. These hormones control bone growth, maintain bone once it is formed, and remodel it.
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
3.6K
Crystal Field Theory - Octahedral Complexes
30.4K
Crystal Field Theory
To explain the observed behavior of transition metal complexes (such as colors), a model involving electrostatic interactions between the electrons from the ligands and the electrons in the unhybridized d orbitals of the central metal atom has been developed. This electrostatic model is crystal field theory (CFT). It helps to understand, interpret, and predict the colors, magnetic behavior, and some structures of coordination compounds of transition metals.
CFT focuses on...
To explain the observed behavior of transition metal complexes (such as colors), a model involving electrostatic interactions between the electrons from the ligands and the electrons in the unhybridized d orbitals of the central metal atom has been developed. This electrostatic model is crystal field theory (CFT). It helps to understand, interpret, and predict the colors, magnetic behavior, and some structures of coordination compounds of transition metals.
CFT focuses on...
30.4K
