目标鱼:基于共识结构的目标预测工具,及其在选择性MAO-B抑制剂发现中的应用
Julián F Fernández1,2, Leandro Martinez Heredia3, Fernando Caracciolo1,2
1Departamento de Quimica Organica, Facultad de Ciencias Exactas, Universidad de Buenos Aires, Intendente Guiraldes 2160, Buenos Aires, Argentina.
Chemistry (Weinheim an der Bergstrasse, Germany)
|October 24, 2024
概括
目标费舍尔是一个新的工具,它结合了分子对接和机器学习来预测生物目标. 这种基于结构的方法有助于药物发现和重新使用,正如确定神经退行性疾病的MAO-B抑制剂所示.
科学领域:
- 计算化学和化学信息学
- 药物发现和药物化学
- 生物信息学和系统生物学
背景情况:
- 确定特定的生物点对于有效的药物发现和重新利用至关重要.
- 现有的目标预测方法在范围或可访问性方面可能受到限制.
- 优化生物测试的使用需要准确预测潜在的分子标.
研究的目的:
- 介绍Target Fisher,一个基于共识结构的目标预测工具.
- 整合分子对接和机器学习,以增强目标识别.
- 提供一个用户友好的网络服务器,用于访问37个蛋白质点的预测.
主要方法:
- 从对接中利用每残留能量分解配置文件作为分子指纹.
- 使用这些指纹来训练特定目标的机器学习模型.
- 开发一个用于可访问预测的Web服务器和37个蛋白质标的精心策划的集合.
主要成果:
- 目标 通过整合对接和机器学习,费舍尔成功预测了潜在的生物目标.
- 一个案例研究证明了该工具在识别神经退行性疾病中选择性抑制单胺氧化酶B (MAO-B) 的有效性.
- 实验验证证证实了已识别的MAO-B抑制剂,展示了该工具的实际实用性.
结论:
- 目标鱼器是有机和药物化学小组在目标识别,药物发现和药物重新用途方面有价值的工具.
- 该工具的基于结构的方法和机器学习集成提供了一个强大的方法来预测药物点.
- 成功识别和验证MAO-B抑制剂突显了Target Fisher在治疗神经退行性疾病方面的实际影响.
相关概念视频
01:49Conserved 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
02:04Protein-protein Interfaces
12.5K
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
12.5K