基于序列的预测,含有非天然氨基酸的的内在可溶性
Marc Oeller1,2, Ryan J D Kang1, Hannah L Bolt3
1Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK.
Nature communications
|November 17, 2023
概括
我们开发了CamSol-PTM,这是一个计算工具,用于预测含有非天然氨基酸的的溶解度. 这种方法快速选成千上万种改性氨基酸变体,加速药物开发.
科学领域:
- 生物化学 生物化学
- 计算生物学 计算生物学
- 药物发现 药物发现 药物发现
背景情况:
- 非天然氨基酸 (mAAs) 对于定制类药物特性,如功能和半衰期至关重要.
- 对含有mAA的的可开发性进行实验性评估是昂贵且耗时的.
- 改性氨基酸 (mAAs) 和翻译后修改 (PTMs) 的化学空间为疗法提供了巨大的潜力.
研究的目的:
- 介绍CamSol-PTM,一种用于预测含有mAA的固有溶解性的计算方法.
- 为了实现快速和可靠的基于序列的可溶性预测,用于开发能力程序.
- 通过计算选大量含有mAA的变体.
主要方法:
- 开发了CamSol-PTM,这是一种基于序列的预测方法,用于测量的内在溶解度.
- 计算选了5万个含有mAA的类型.
- 对含有五种不同小尺寸mAAs的37种变体进行实验验证的溶解性.
主要成果:
- 卡姆索尔-PTM准确地预测了含有mAAs的的可溶性.
- 计算选扩大了对溶性化学空间的探索,超过了四个数量级.
- 与实验溶解度测量对比的验证预测,证实方法的准确性.
结论:
- 卡姆索尔-PTM促进了含有mAA的的快速和经济有效的开发能力评估.
- 计算选显著提高了在设计中的可溶性探索.
- 该CamSol-PTM网络服务器可供公众使用,以帮助类药物开发.
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
01:25Protein Folding
8.1K
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...
8.1K
03:42Amino acids
89.0K
Amino acids are the monomers that comprise proteins. Each amino acid has the same fundamental structure, which consists of a central carbon atom, or the alpha (α) carbon, bonded to an amino group (NH2), a carboxyl group (COOH), and to a hydrogen atom. Every amino acid also has another atom or group of atoms bonded to the central atom known as the R group. There are 20 common amino acids present in proteins, each with a different R group. Variation in the amino acid sequence is responsible...
89.0K