蛋白质稳态与动态结构的理性设计

祝诚研究组综合运用生物化学、生物物理等实验技术，结合计算机辅助设计、分子动力学模拟等计算方法，理性设计与改造蛋白质分子的结构与功能，为更精确的抗体设计、酶的改性、正交化生物体系的构建提供新方法和新元件。

1、蛋白质稳态结构的设计，赋予多种蛋白质骨架全新的功能

人工智能驱动的双功能分子序列设计 (eLife 2024)

连续结构片段嫁接（Nature Communications 2019, Methods in Molecular Biology 2017）

分离活性位点嫁接（Protein Science 2016, Protein & Cell 2011）

2、蛋白质动态构象的设计，开发非稳态结构捕捉与调控方法

蛋白质解折叠中间体（PNAS 2018, Structure 2016）

蛋白质折叠过渡态（Biophysical J 2013）膜蛋白激活态（Proteins 2019）

3、动力学模拟解析复杂生命分子的构造规律

合作发表：蛋白质-蛋白质 (Cell Host&Microbe 2024) 蛋白质-核酸（Immunity 2019, PAIN 2023, iScience 2024）蛋白质-气体 (Nature Cell Biology 2022)  蛋白质-高分子聚合物（Nature Communications 2022）蛋白质-小分子（Microbiology Spectrum 2021）小分子-膜 (Advanced Science 2023) 多肽-膜 (Frontiers in Immunology 2022)  膜蛋白 (Cell Discovery 2024) 蛋白质-无机纳米粒子 (Frontiers in Molecular Biosciences 2021)

承担科研项目

科技部 国家重点研发计划 细胞代谢的人工智能调控技术 （课题负责人）

国家自然科学基金 面上项目 理性设计别构调控的蛋白质活性开关 （主持）

国家自然科学基金 青年项目 理性设计表位嫁接的HIV-1 Env蛋白质抗原 （主持）

国家自然科学基金 原创探索计划项目 未来生物技术（参与）

科技部 国家重点研发计划 正交化蛋白质元件的人工设计与构建 （参与）

天津大学 自主创新基金 冠状病毒复制启动蛋白的动力学与进化模式研究 （主持）

重点产业链应用场景示范项目 西安  基于人工智能方法设计合成抗微生物肽 （参与）

研究应用 

HIV-1新型抗原：Science Daily  渐冻症与SOD1蛋白质聚集：F1000 Recommendation  多肽抗菌/抗病毒机制模拟：Frontiers  磷酸酶如何感知CO2: Intrinsically disordered CO2 sensors  膜融合脂质体如何递送物质入细胞: Advanced Science封面

专利

末端脱氧核苷酸转移酶突变体及其应用、miRNA 检测方法

抗微生物肽Perceptide-TJ-2及其在制备广谱抗病毒药物中的用途(ZL 2023 1 0894433.5)

一种抗菌肽及其在制备抗菌药物或抗病毒药物中的应用

• 蛋白质设计
  蛋白质设计为人们创造可预测、可改造的人工生物体系提供了结构基石与功能模块，为资源、健康、和环境等全球性问题提供颠覆性的解决方案。蛋白质设计融合了分子力场、计算模拟与生物物理等手段, 通过解析复杂生命分子的构造规律, 实现结构与功能的理性改造与构建。
• 分子模拟
  结合结构生物学和分子动力学模拟等技术, 充分表征人工设计蛋白质元件的稳态结构与动力学特征，并通过生物化学与细胞生物学实验验证理性设计的新功能元件。祝诚研究组基于分子动力学模拟研究了蛋白质热力学稳定性、蛋白-小分子/核酸/纳米粒子等体系的作用特征。

• 2023 天津大学本科生毕业设计优秀指导教师
• 2020 第一届生物设计研究国际会议 海报一等奖
• 2019 天津大学 北洋学者英才计划
• 2015 北卡罗来纳大学教堂山 本科生优秀导师奖
• 2012 北京大学 定量生物学研究生奖学金
• 2004 南京大学 人民奖学金一等奖

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