利用 ProteinMPNN 改进蛋白质表达、稳定性和功能

IF 14.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Kiera H. Sumida, Reyes Núñez-Franco, Indrek Kalvet, Samuel J. Pellock, Basile I. M. Wicky, Lukas F. Milles, Justas Dauparas, Jue Wang, Yakov Kipnis, Noel Jameson, Alex Kang, Joshmyn De La Cruz, Banumathi Sankaran, Asim K. Bera, Gonzalo Jiménez-Osés and David Baker*, 
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引用次数: 0

摘要

天然蛋白质的功能已得到高度优化,但由于在异源系统中的表达能力较差、溶解度有限以及对温度的敏感性,通常难以生产出适合生物技术应用的规模。因此,一种既能改善原生蛋白质的物理特性,又能保持其功能的通用方法对基于蛋白质的技术具有广泛的实用性。在这里,我们展示了深度神经网络 ProteinMPNN 与进化和结构信息相结合,为提高蛋白质的表达、稳定性和功能提供了一条途径。对于肌红蛋白和烟草蚀刻病毒(TEV)蛋白酶,我们设计出了具有更高的表达量、更高的熔化温度和更好的功能的产品。对于 TEV 蛋白酶,与母序列和以前报道的 TEV 变体相比,我们发现了多种催化活性更强的设计。我们的方法对于改善具有重要生物技术意义的蛋白质的表达、稳定性和功能具有广泛的用途。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Improving Protein Expression, Stability, and Function with ProteinMPNN

Improving Protein Expression, Stability, and Function with ProteinMPNN

Improving Protein Expression, Stability, and Function with ProteinMPNN

Natural proteins are highly optimized for function but are often difficult to produce at a scale suitable for biotechnological applications due to poor expression in heterologous systems, limited solubility, and sensitivity to temperature. Thus, a general method that improves the physical properties of native proteins while maintaining function could have wide utility for protein-based technologies. Here, we show that the deep neural network ProteinMPNN, together with evolutionary and structural information, provides a route to increasing protein expression, stability, and function. For both myoglobin and tobacco etch virus (TEV) protease, we generated designs with improved expression, elevated melting temperatures, and improved function. For TEV protease, we identified multiple designs with improved catalytic activity as compared to the parent sequence and previously reported TEV variants. Our approach should be broadly useful for improving the expression, stability, and function of biotechnologically important proteins.

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来源期刊
CiteScore
24.40
自引率
6.00%
发文量
2398
审稿时长
1.6 months
期刊介绍: The flagship journal of the American Chemical Society, known as the Journal of the American Chemical Society (JACS), has been a prestigious publication since its establishment in 1879. It holds a preeminent position in the field of chemistry and related interdisciplinary sciences. JACS is committed to disseminating cutting-edge research papers, covering a wide range of topics, and encompasses approximately 19,000 pages of Articles, Communications, and Perspectives annually. With a weekly publication frequency, JACS plays a vital role in advancing the field of chemistry by providing essential research.
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