Simultaneous enhancement of multiple functional properties using evolution-informed protein design

• 全文链接

利用进化信息进行蛋白设计同时增强多种功能性质

关键词：

来源：

Nature Communications

全文链接：

//agri.nais.net.cn/topic/downloadFile/23219715-3c06-4601-8f0a-1166edfe769e

来源地址：

https://www.nature.com/articles/s41467-024-49119-x#Sec9

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：

2024-06-20

摘要：

A major challenge in protein design is to augment existing functional proteins with multiple property enhancements. Altering several properties likely necessitates numerous primary sequence changes, and novel methods are needed to accurately predict combinations of mutations that maintain or enhance function. Models of sequence co-variation (e.g., EVcouplings), which leverage extensive information about various protein properties and activities from homologous protein sequences, have proven effective for many applications including structure determination and mutation effect prediction. We apply EVcouplings to computationally design variants of the model protein TEM-1 β-lactamase. Nearly all the 14 experimentally characterized designs were functional, including one with 84 mutations from the nearest natural homolog. The designs also had large increases in thermostability, increased activity on multiple substrates, and nearly identical structure to the wild type enzyme. This study highlights the efficacy of evolutionary models in guiding large sequence alterations to generate functional diversity for protein design applications.