北京大學定量生物學中心

學術報告 

題    目: Computational Protein Design for Immunotherapy and Immune Modulation

報告人: 楊為 博士

深圳醫學科學院 特聘研究員

時   間: 6月10日（周二）13:30-14:30

地   點: 呂志和樓B101

主持人: 來魯華 教授

摘要:

Immune receptors have emerged as critical therapeutic targets for cancer immunotherapy. Designed protein binders can have high affinity, modularity, and stability and hence could be attractive components of protein therapeutics directed against these receptors, but traditional Rosetta based protein binder methods using small globular scaffolds have difficulty achieving high affinity on convex targets. Here we describe the development of helical concave scaffolds tailored to the convex target sites typically involved in immune receptor interactions. We employed these scaffolds to design proteins that bind to TGFβRII, CTLA-4, and PD-L1, achieving low nanomolar to picomolar affinities and potent biological activity following experimental optimization. Co-crystal structures of the TGFβRII and CTLA-4 binders in complex with their respective receptors closely match the design models. These designs should have considerable utility for downstream therapeutic applications.

報告人簡介：

楊為博士，于2019年獲得清華大學博士學位，師從來魯華教授。2019至2025年在美國華盛頓大學蛋白質設計研究所從事博士後研究工作，師從2024年諾貝爾化學獎獲得者David Baker教授。2025年6月，楊為博士全職加入深圳醫學科學院，任職特聘研究員。楊為博士專注于開發全新蛋白質-蛋白質相互作用計算設計方法，及其在免疫調控和腫瘤免疫治療領域的應用，主要研究成果包括：設計了具有凹型結構的蛋白質骨架，解決了為凸型蛋白質表面設計全新結合蛋白的難題，成功設計了具有高穩定性，超高親和力的免疫檢查點受體結合蛋白（Nature Communications 2025）；設計并驗證了具有動态結構的細胞因子，使其親和力和生物活性受細胞表面特異性表達受體調控以降低系統毒性；開發了從頭設計D-型螺旋結合肽的計算設計方法，從頭設計并驗證了由D-型氨基酸組成的與TNFα結合的螺旋肽（FEBS letters 2019）。