DeCOIL:优化退化子库用于机器学习辅助的蛋白质工程
Jason Yang1, Julie Ducharme1, Kadina E Johnston2
1Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.
ACS synthetic biology
|July 31, 2023
概括
我们开发了一种新方法,DeCOIL,以创建具有成本效益的退化编码子库,用于机器学习辅助的蛋白质工程. 这种方法优化了图书馆,以有效地探索具有高适应性和多样性的蛋白质变体.
科学领域:
- 生物技术是生物技术.
- 计算生物学 计算生物学
- 蛋白质工程是指蛋白质工程.
背景情况:
- 机器学习 (ML) 通过提出蛋白质变体来推进蛋白质工程.
- 合成大型变体库是一个昂贵的瓶.
- 退化子 (DC) 图书馆提供了一个具有成本效益的突变发生策略.
研究的目的:
- 开发一种优化的计算方法,用于设计针对ML辅助蛋白质工程的DC库.
- 为了使高适应性和序列多样性的蛋白质变体能够有效地探索.
主要方法:
- 介绍了Degenerate Codon Optimization for Informed Libraries (DeCOIL),这是DC库优化的一个通用化方法.
- 使用计算模拟和实验湿实验室研究验证DeCOIL.
- 为实施DeCOIL开发了配套的开源软件.
主要成果:
- DeCOIL有效地优化了用于ML辅助蛋白质工程的DC库.
- 该方法在两个不同的案例研究中取得了成功.
- 通过DeCOIL,可以采样具有所需高适应性和多样性的蛋白质变体.
结论:
- DeCOIL解决了蛋白质工程中DC库设计现有方法的局限性.
- 该方法是直接的,用户友好,可通用和可扩展的.
- DeCOIL促进了基于信息的库的生成,以有效地探索蛋白质序列空间.
相关概念视频
From DNA to Protein
18.6K
The flow of genetic information in cells from DNA to mRNA to protein is described by the central dogma, which states that genes specify the sequence of mRNAs, which in turn specify the sequence of amino acids making up all proteins. The decoding of one molecule to another is performed by specific proteins and RNAs. Because the information stored in DNA is so central to cellular function, it makes intuitive sense that the cell would make mRNA copies of this information for protein synthesis...
18.6K
Improving Translational Accuracy
11.6K
Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
11.6K
Conservation of Protein Domains Over Different Proteins
10.9K
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
10.9K
The Central Dogma
127.0K
Overview
127.0K
Leaky Scanning
5.2K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.2K
Conservation of Protein Domains
3.1K
3.1K


