北京大学定量生物学中心

学术报告 

题    目: Computational Protein Design for Immunotherapy and Immune Modulation

报告人: 杨为 博士

深圳医学科学院 特聘研究员

时   间: 6月10日（周二）13:30-14:30

地   点: 吕志和楼B101

主持人: 来鲁华 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.

报告人简介：

杨为博士，于2019年获得清华大学博士学位，师从来鲁华教授。2019至2025年在美国华盛顿大学蛋白质设计研究所从事博士后研究工作，师从2024年诺贝尔化学奖获得者David Baker教授。2025年6月，杨为博士全职加入深圳医学科学院，任职特聘研究员。杨为博士专注于开发全新蛋白质-蛋白质相互作用计算设计方法，及其在免疫调控和肿瘤免疫治疗领域的应用，主要研究成果包括：设计了具有凹型结构的蛋白质骨架，解决了为凸型蛋白质表面设计全新结合蛋白的难题，成功设计了具有高稳定性，超高亲和力的免疫检查点受体结合蛋白（Nature Communications 2025）；设计并验证了具有动态结构的细胞因子，使其亲和力和生物活性受细胞表面特异性表达受体调控以降低系统毒性；开发了从头设计D-型螺旋结合肽的计算设计方法，从头设计并验证了由D-型氨基酸组成的与TNFα结合的螺旋肽（FEBS letters 2019）。