Opportunities and challenges in design and optimization of protein function

蛋白质功能设计与优化的机遇与挑战

关键词：

来源：

Nature Reviews Molecular Cell Biology

来源地址：

https://www.nature.com/articles/s41580-024-00718-y

资源所属：

饲料用酶工程

类型：

学术文献

语种：

英语

原文发布日期：

2024-04-02

摘要：

The field of protein design has made remarkable progress over the past decade. Historically, the low reliability of purely structure-based design methods limited their application, but recent strategies that combine structure-based and sequence-based calculations, as well as machine learning tools, have dramatically improved protein engineering and design. In this Review, we discuss how these methods have enabled the design of increasingly complex structures and therapeutically relevant activities. Additionally, protein optimization methods have improved the stability and activity of complex eukaryotic proteins. Thanks to their increased reliability, computational design methods have been applied to improve therapeutics and enzymes for green chemistry and have generated vaccine antigens, antivirals and drug-delivery nano-vehicles. Moreover, the high success of design methods reflects an increased understanding of basic rules that govern the relationships among protein sequence, structure and function. However, de novo design is still limited mostly to α-helix bundles, restricting its potential to generate sophisticated enzymes and diverse protein and small-molecule binders. Designing complex protein structures is a challenging but necessary next step if we are to realize our objective of generating new-to-nature activities.