张鲁嘉课题组(Lujia·Lab)依托“华东师范大学化学与分子工程学院”及“纽约大学(上海)理论与计算化学中心”于2016年11月组建。主要研究方向为酶分子动态机制解析、精准设计及应用开发。酶是典型功能性生物大分子,是绝大多数生命过程的催化基础,深入解析其动态催化机制对生命过程的认知、疾病的产生和诊断及治疗方法的研究具有重大意义。同时酶是绿色生物合成中“芯片”级的核心,精确设计符合工业生产需求的酶在化学化工、生物医药、轻工食品等领域均具有巨大价值。酶是由数万原子组成的生物大分子来完成量子层面的化学反应催化,涉及复杂的物理、化学、以及生物过程,意义重大但极具挑战性,是科学研究的热点和难点。
课题组在国内最早开展酶等蛋白质功能设计研究,目前已经建成从结构认知–机制解析–精准设计–应用开发的完整研究体系,充分融合理论计算、人工智能、生物化学、合成生物、化学催化等多学科技术手段,全方面开展相关研究。课题组目前已经搭建了干、湿实验结合的完备研究平台。干实验部分,实验室拥有10余节点的CPU和GPU计算集群,并且在天河二号等国家大型计算机组上拥有账号,部署了Schrodinger, Amber, Gromacs, Gaussian 等多个量子化学及分子动力学计算软件,以及课题组自行开发的ETSS、ESDS等酶分子设计软件。湿实验部分的拥有PCR、AKTA蛋白纯化仪器、多层摇床、无氧反应器、HPLC、P2标准生物安全实验室、二氧化碳摇床等研究生物学、同时共享使用的华东师范大学和纽约大学冷冻电镜设备平台。主要研究内容包括:
A. 基于蛋白质结晶、冷冻电镜的高分辨率蛋白质结构解析及催化反应关键过渡态捕捉。
B. 融合理论计算和人工智能的蛋白质量子计算、分子模拟和精准设计理论与工具开发。
C. 大肠杆菌、枯草芽孢杆菌、酵母、昆虫及哺乳动物细胞等真、原核表达系统的构建。
D. 合成生物学、绿色生物转化过程的分子基础认知、高性能酶分子设计及工业应用开发。
E. 蛋白质分子设计应用:人工蛋白材料的分子设计、抗体疫苗的结构功能机制解析及分子设计。
Lujia·Lab was established in November 2016 relying on School of Chemistry and Molecular Engineering of East China Normal University and Center for Theoretical and Computational Chemistry of New York University Shanghai. The main research interests of Lujia·Lab are enzyme dynamic mechanism analysis, accurate design and application development. Enzymes are typical biomacromolecules, functioning the catalysis in most of the life processes. Therefore, having a deep understanding about their catalytic mechanisms is of great significance for the cognition of living processes, causes of diseases, and the research on diagnosis and treatment methods. Meanwhile, enzymes are at the heart of green biosynthesis, similar to the chips in electrical devices. Precisely designing enzymes that meet the needs of industrial production weighs great value in the fields of chemical engineering, biomedicine, and food industry. The chemical reactions catalyses achieved by enzymes containing millions of atoma at the quantum level, involve complex physical, chemical, and biological processes, which makes the research significant but extremely challenging, and a hot but difficult area in frontier study.
Lujia·Lab is the first to focus on the functional design of enzymes and other proteins in China. Up to now, we have built a complete research system of structural cognition – mechanism analysis – accurate design – application development, fully integrating theoretical calculations, artificial intelligence, biochemistry, synthetic biology, chemical catalysis, and other multidisciplinary technical means to carry out relevant research in all aspects. A perfect platform combining theoretical calculations and practical experiments has been established. For theoretical calculations, the laboratory has more than 10 nodes of CPU and GPU computing clusters, and owns accounts on national large-scale computer groups such as Tianhe-2. We also deploy a number of quantum chemistry and molecular dynamics calculation softwares such as Schrodinger, Amber, Gromacs, Gaussian, etc., as well as ETSS, ESDS and other enzyme molecular design software developed by the research group. For practical experiments, Lujia·Lab equips with PCR, AKTA protein purification instrument, multi-layer shaker, anaerobic reactor, HPLC, P2 standard biosafety laboratory, carbon dioxide shaker, and shares cryo-electron microscopy platform of East China Normal University and New York University Shanghai. The main research contents listed as follows:
A. High-resolution protein structure analysis and key transition state capture of catalytic reactions based on protein crystallization and cryo-electron microscopy.
B. Development of protein quantum computing, molecular simulation and precise design theory and tools that integrate theoretical calculation and artificial intelligence.
C. Construction of eukaryotic and prokaryotic expression systems for Escherichia coli, Bacillus subtilis, yeast, insect and mammalian cells.
D. Synthetic biology, molecular basic cognition of green biotransformation process, high-performance enzyme molecular design and industrial application development.
E. Application of protein molecular design: molecular design of artificial protein materials, structural and functional mechanism analysis and molecular design of antibody vaccines.
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