通过专家指导的深度学习,推进NanoLuc Luciferase稳定性超越定向进化和理性设计.
Spencer Gardiner1, Joseph Talley2, Tyler Green2
1Department of Physics and Astronomy, Brigham Young University, Provo, Utah 84602, United States.
概括
研究人员通过混合深度学习和结构引导设计方法增强了NanoLuc luciferase (NLuc) 的热稳定性. 这可以在更高的温度下改善酶活性,用于先进的生物发光应用.
科学领域:
- 生物化学 生物化学
- 蛋白质工程是指蛋白质工程.
- 分子生物学分子生物学
背景情况:
- 工程光酶对于生物成像和传感至关重要.
- 优化NanoLuc luciferase (NLuc) 很难,因为稳定性-活性权衡和低序列同质性.
- 现有的方法在NLuc增强方面遇到了困难.
研究的目的:
- 开发增强的NanoLuc luciferase (NLuc) 变体,在高温下提高热稳定性和活性.
- 克服传统蛋白质工程方法对NLuc.Luc的局限性.
- 介绍一种用于酶工程的新型混合方法.
主要方法:
- 集成的深度学习与结构引导的理性设计.
- 系统地分析工程NLuc变体库.
- 利用分子动力学模拟和蛋白质折叠研究.
主要成果:
- 开发了增强的NLuc变种 (B.07和B.09),显著增加了热稳定性 (7.2°C和5.1°C化温度增加).
- 在高温下表现出持续的酶活性.
- 确定了关键突变部位 (末端,远端环节),可以在不破坏功能的情况下增强热弹性.
结论:
- 混合方法成功设计了热稳定的NLuc变种.
- 远距离区域的修改,同时保持全网络,提高了热弹性.
- 这种方法为具有稳定性-活性约束的工程酶提供了强大的框架.
相关概念视频
The Evidence for Evolution
48.4K
Genetic variations accumulating within populations over generations give rise to biological evolution. Evolutionary changes can result in the formation of novel varieties and entire new species. These changes are responsible for the diverse forms of life inhabiting the planet. The evidence for evolution suggests that all living organisms descended from common ancestors.
48.4K
Convergent Evolution
33.1K
Evolution shapes the features of organisms over time, ensuring that they are suited for the environments in which they live. Sometimes, selection pressure leads to the rise of similar but unrelated adaptations in organisms with no recent common ancestors, a process known as convergent evolution.
33.1K
Rationalizing Substitutions
62
Integrals involving non-rational functions are often difficult to evaluate using standard techniques, especially when radicals appear in the integrand. Rationalizing substitution provides a systematic method for simplifying such integrals by converting them into rational forms that are easier to handle.Consider a rod whose linear mass density depends on a constant linear density, a characteristic length, and the distance from the left end of the rod. Determining the total mass requires...
62
Rational Expressions
412
Rational expressions are algebraic fractions in which both the numerator and the denominator are polynomials. These expressions follow the arithmetic rules of numerical fractions but require extra care due to the presence of variables. A fundamental part of working with rational expressions is identifying values that make the expression undefined, typically those that result in division by zero or undefined radicals.Determining the DomainThe domain of a rational expression includes all real...
412
Asymptotes in Rational Functions
269
A rational function is defined as the quotient of two polynomials: where Q(x)≠0, These functions often exhibit asymptotes, which are the lines that the graph approaches but never touches. These asymptotes are classified based on how the function behaves near specific values of the input.Vertical asymptotes occur where the denominator is zero, and the numerator is not, causing the function to be undefined. These are found by solving Q(x)=0. For example: has a vertical...
269
Nuclear Stability
23.4K
Protons and neutrons, collectively called nucleons, are packed together tightly in a nucleus. With a radius of about 10−15 meters, a nucleus is quite small compared to the radius of the entire atom, which is about 10−10 meters. Nuclei are extremely dense compared to bulk matter, averaging 1.8 × 1014 grams per cubic centimeter. If the earth’s density were equal to the average nuclear density, the earth’s radius would be only about 200 meters.
To hold positively charged protons together...
To hold positively charged protons together...
23.4K


