《生命科学》 2021, 33(12): 1436-1444

合成生物学中蛋白质计算预测设计的应用与发展

孙瑨原^1,2 , 崔颖璐¹ , 吴　边^1,*

¹中国科学院微生物研究所，中国科学院微生物生理与代谢工程重点实验室，微生物资源前期 开发国家重点实验室，北京 100101 ²中国科学院大学生命科学学院，北京 100049

摘　要：

合成生物学以“工程化”为核心指导思想，自下而上开发生物技术来解决人类社会面临的重大挑战。蛋白质作为生命活动的直接执行者和合成生物学中关键的底层元件，对其定量认识和工程改造的能力直接影响合成生物学的上层建筑。通过蛋白质计算设计技术可实现功能空间跳跃，为合成生物学提供全新元件，使序列- 结构- 功能的研究从“格物致知”转化为“建物致知”的新范式。该文介绍了在蛋白质序列- 结构-功能的预测和设计中采用的前沿技术和应用进展，讨论了蛋白质计算设计面临的科学挑战，并提出了应对挑战应优先发展的研究方向。

通讯作者：吴　边 , Email:wub@im.ac.cn

Application and development trend of computational protein prediction and design in synthetic biology

SUN Jin-Yuan^1,2 , CUI Ying-Lu¹ , WU Bian^1,*

¹CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China ²University of Chinese Academy of Sciences, Beijing 100101, China

Abstract:

Synthetic biology relies on core principles of engineering and offers a bottom-up approach to use and build upon our vast leaps in the molecular understanding of biological systems to address challenges facing today's society. As the direct executor of life activities, proteins are essential building blocks in synthetic biology. The quantitative understanding and engineering capabilities of them directly affect the superstructure of synthetic biology. Through computational protein design, sequence jump along the fitness landscape would be achieved and provide new building blocks for synthetic biology. A paradigm shift of the study of sequence-structure-function occurs from "observe to understand" to "build to understand". Here, we reviewed the studies following the concept of “build to understand” to predict and design protein structure and function by computational protein design and the applications of this state-of-the-art method. The challenges faced by computational protein design and the proposed solutions are also discussed.

Communication Author：WU Bian , Email:wub@im.ac.cn