By constructing mutant libraries and utilizing high-throughput screening methods, directed evolution has emerged as the most popular strategy for protein design nowadays. In the past decade, taking advantages of computer performance and algorithms, computer-assisted protein design has rapidly developed and become a powerful method of protein engineering. Based on the simulation of protein structure and calculation of energy function, computational design can alter the substrate specificity and improve the thermostability of enzymes, as well as de novo design of artificial enzymes with expected functions. Recently, machine learning and other artificial intelligence technologies have also been applied to computational protein engineering, resulting in a series of remarkable applications. Along the lines of protein engineering, this paper reviews the progress and applications of computer-assisted protein design, and current trends and outlooks of the development.
定向进化通过建立突变体文库与高通量筛选方法，快速提升蛋白的特定性质，是目前蛋白质工程最为常用的蛋白质设计改造策略。近十年随着计算机运算能力大幅提升以及先进算法不断涌现，计算机辅助蛋白质设计改造得到了极大的重视和发展，成为蛋白质工程新开辟的重要方向。以结构模拟与能量计算为基础的蛋白质计算设计不但能改造酶的底物特异性与热稳定性，还可从头设计具有特定功能的人工酶。近年来机器学习等人工智能技术也被应用于计算机辅助蛋白质设计改造，并取得瞩目的成绩。文中介绍了蛋白质工程的发展历程，重点评述当前计算机辅助蛋白质设计改造方面的进展与应用，并展望其未来发展方向。.
Keywords: artificial intelligence; computational design; energy function; protein engineering; simulation of structure.