糖聚合物结构的贝叶斯优化,用于与霍乱毒素B子单元的相互作用
Masanori Nagao1, Osuke Nakahara1, Xincheng Zhou1
1Department of Chemical Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan. miuray@chem-eng.kyushu-u.ac.jp.
Nanoscale
|May 31, 2024
概括
研究人员优化了合成甘油聚合物以模仿GM1结构. 表现最好的甘油聚合物表现出强烈的结合霍乱毒素B亚单元 (CTB),表明治疗应用的潜力.
科学领域:
- 碳水化合物化学 碳水化合物化学
- 生物材料科学 生物材料科学
- 计算化学的计算化学
背景情况:
- 甘胺GM1在细胞过程和病原体相互作用中起着至关重要的作用.
- 合成甘油聚合物为模仿天然碳水化合物结构提供了一个多功能平台.
- 霍乱毒素B亚单元 (CTB) 是开发抑制剂的关键目标,因为它在霍乱病原发生中的作用.
研究的目的:
- 确定合成甘油聚合物的最佳成分,以模仿GM1.
- 识别具有增强结合亲和力与霍乱毒素B亚单元 (CTB) 的糖聚合物.
主要方法:
- 贝叶斯优化被用来有效地探索糖聚合物的结构空间.
- 酶相关免疫吸收试验 (ELISA) 用于量化糖聚合物和CTB之间的结合相互作用.
- 用高斯过程回归来预测基于实验数据的最佳糖聚合物成分.
主要成果:
- 发现最优的糖聚合物组成是60mol%的银河糖和25mol%的神经胺酸.
- 这种优化的甘油聚合物在CTB抑制方面显示了75μM的低IC50值.
- 该研究成功地确定了一种具有显著增强结合CTB的合成甘油聚合物.
结论:
- 合成甘油聚合物可以有效地优化以模仿GM1结构.
- 鉴定到的甘油聚合物成分对CTB具有很高的亲和力,这表明它有可能作为治疗剂.
- 贝叶斯优化是一个强大的工具,可以加速功能性甘氨酸结合物的设计.
相关概念视频
02:34Structural Isomerism
Isomerism in Complexes
Isomers are different chemical species that have the same chemical formula. Structural isomerism of coordination compounds can be divided into two subcategories, the linkage isomers and coordination-sphere isomers.
Linkage isomers occur when the coordination compound contains a ligand that can bind to the transition metal center through two different atoms. For example, the CN− ligand can bind through the carbon atom or through the nitrogen atom. Similarly, SCN− can be...
Isomers are different chemical species that have the same chemical formula. Structural isomerism of coordination compounds can be divided into two subcategories, the linkage isomers and coordination-sphere isomers.
Linkage isomers occur when the coordination compound contains a ligand that can bind to the transition metal center through two different atoms. For example, the CN− ligand can bind through the carbon atom or through the nitrogen atom. Similarly, SCN− can be...
02:15Protein and Protein Structure
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 can...
A protein's shape is critical to its function. For example, an enzyme can...
02:35Noncovalent Attractions in Biomolecules
Noncovalent attractions are associations within and between molecules that influence the shape and structural stability of complexes. These interactions differ from covalent bonding in that they do not involve sharing of electrons.
Four types of noncovalent interactions are hydrogen bonds, van der Waals forces, ionic bonds, and hydrophobic interactions.
Hydrogen bonding results from the electrostatic attraction of a hydrogen atom covalently bonded to a strong-electronegative atom like oxygen,...
Four types of noncovalent interactions are hydrogen bonds, van der Waals forces, ionic bonds, and hydrophobic interactions.
Hydrogen bonding results from the electrostatic attraction of a hydrogen atom covalently bonded to a strong-electronegative atom like oxygen,...
01:25Drug-Receptor Bonds
Drug-receptor bonds are formed through various chemical forces when drugs interact with target cells. Covalent bonds, strong and irreversible, are exemplified by DNA-alkylating anticancer agents that inhibit cell division. However, such irreversible drug binding lacks selectivity and can modify the DNA of the surrounding healthy cells. Covalent binding often contributes to tissue toxicity, as seen with chloroform and paracetamol metabolites binding to the liver, causing hepatotoxicity.
In...
In...
01:16Adrenergic Agonists: Chemistry and Structure-Activity Relationship
Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of the aromatic...
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of the aromatic...
01:28Structure-Activity Relationships and Drug Design
Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence its...
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence its...