刘思睿，助理教授，博士生导师

邮箱： liusirui@pku.edu.cn

教育经历

2010.09-2014.07：北京大学化学院，化学&数学（双学位）学士

2014.09-2019.07：北京大学化学院，物理化学博士，导师：高毅勤教授

工作经历

2019.09-2022.01：哈佛大学，博士后，合作导师：Dr. Sergey Ovchinnikov

2022.02-2026.06：昌平实验室，研究员

2026.07  - ：   北京大学药学院，助理教授

研究方向：

在生物大分子药物研发中，理解其结构与活性的关系是发现靶点和改进其活性等功能特性的关键。刘思睿博士主要研究领域为计算生物学与计算化学，致力于融合物理-表征实验先验和深度学习方法以准确预测生物分子体系多尺度结构及构象动态。近年来主要在以下三个方向展开探索：1). 建设基础结构预测模型与应用生态：搭建自有数据集与国产基础模型并获评“2021年软件行业典型示范案例”，推动实验-计算互利共生；2). 发展复杂生物分子体系深度学习整合建模工具：开发核磁、化学交联、电镜等多实验联用的复杂蛋白及蛋白-核酸体系整合建模及构象生成方法，提高结构预测精度与构象预测广度；3). 开发多用途深度学习蛋白应用框架：发展实用应用框架，推动基础模型在实验约束复合物结构预测、蛋白多构象挖掘与新蛋白发现等领域的应用。相关工作以一作或通讯（含共同）在Nature Methods、Nature Machine Intelligence、Nucleic Acids Research等期刊发表，被Nature Methods杂志专题报道，论文总引用1600余次，申请专利5项。

研究兴趣：

1) 复杂多分子体系结构/构象预测与应用：以蛋白为核心、拓展至核酸与小分子体系的结构与构象预测和物理化学空间采样，探索新靶点与新互作机制；

2) 生化实验技术与深度学习模型的融合迭代：整合深度学习方法和包括但不限于冷冻电镜、NMR、（交联）质谱等结构表征实验技术，开发实验-计算联用新策略；

3) 药物分子对接与设计：以蛋白为核心的多类型靶点大小分子药物快速筛选与迭代设计，探索并扩展可成药空间。

代表性论文：

*equal contribution, #corresponding author(s)

1. Y. Xie*, C. Zhang*, S. Li, X. Du, Y. Lu, M. Wang, Y. Hu, Z. Chen, S. Liu#, Y. Q. Gao#. Integrating diverse experimental information to assist protein complex structure prediction by GRASP. Nature Methods 22, 2362–2374 (2025).

2. S. Feng*, Z. Chen*, C. Zhang, Y. Xie, S. Ovchinnikov#, Y.Q. Gao#, S. Liu#. Integrated structure prediction of protein–protein docking with experimental restraints using ColabDock. Nature Machine Intelligence 6 (8), 924-935 (2024).

3. S. Li, C. Zhang, L. Kong, Y. Xue, S. Liu#, Y. Q. Gao#. Disentangling coevolutionary constraints for modeling protein conformational heterogeneity. Communications Chemistry 9, 146 (2026).

4. S. Liu#, H. Chu, Y. Xie, F. Wu, F. Mu, J. Wei, N. Ni, C. Wang, J. Zhang, M. Chen, J. Li, F. Yu, H. Fu, S. Wang, C. Tian, Z. Wang#, Y. Q. Gao#. Assisting and accelerating NMR assignment with restrained structure prediction. Communications Biology 8, 1067 (2025).

5. G. A. Pavlopoulos#, F. A. Baltoumas*, S. Liu, O. Selvitopi, A. P. Camargo, S. Nayfach, A. Azad, S. Roux, L. Call, N. N. Ivanova, I. M. Chen, D. Paez-Espino, E. Karatzas, I. Iliopoulos, K. Konstantinidis, J. M. Tiedje, J. Pett-Ridge, D. Baker, A. Visel, C. A. Ouzounis, S. Ovchinnikov, A. Buluç, N. C. Kyrpides#. Unraveling the functional dark matter through global metagenomics. Nature 622 (7983), 594-602 (2023).

6. S. Liu*, J. Zhang*, H. Chu*, M. Wang, B. Xue, N. Ni, J. Yu, Y. Xie, Z. Chen, M. Chen, Y. Liu, P. Patra, F. Xu, J. Chen, Z. Wang, L. Yang, F. Yu#, L. Chen#, Y. Q. Gao#. PSP: million-level protein sequence dataset for protein structure prediction. arXiv. arXiv:2206.12240 (2022).

7. H. Quan*, H. Tian*, S. Liu*, Y. Xue, Y. Zhang, W. Xie, and Y. Q. Gao#. Progressive Domain Segregation in Early Embryonic Development and Underlying Correlation to Genetic and Epigenetic Changes. Cells. 10(10):2521 (2021)

8. S. Liu, H. Wang, I. Anishchenko, J. Dauparas, S. Ovchinnikov#. Towards an end to end structure prediction pipeline. CASP14 Abstract Book (2020).

9. S. Liu*, L. Zhang*, H. Quan*, H. Tian, L. Meng, L. Yang, H. Feng, and Y. Q. Gao#. From 1D sequence to 3D chromatin dynamics and cellular functions: a phase separation perspective. Nucleic Acids Res. 46, 9367 (2018).

10. W. J. Xie*, L. Meng*, S. Liu*, L. Zhang, X. Cai, Y. Q. Gao#. Structural modeling of chromatin integrates genome features and reveals chromosome folding principle. Sci. Rep. 7, 2818 (2017).

11. A. A. Agbleke*, A. Amitai*, J. D. Buenrostro*, A. Chakrabarti*, L. Chu*, A. S. Hansen*, K. M. Koenig*, A. S. Labade*, S. Liu*, T. Nozaki*, S. Ovchinnikov*, A. Seeber*, H. A. Shaban*, J.-H. Spille*, A. D. Stephens*, J.-H. Su*, D. Wadduwage*. Advances in Chromatin and Chromosome Research: Perspectives from Multiple Fields. Mol. Cell. 79(6), 881 (2020). (Review)

12. S. Liu, H. Quan, H. Tian, R. Zhou, L. Yang, Y. Q. Gao#. 1D sequence based 3D chromatin phase separation: Forces, processes, and functions. Acta Physico-Chimica Sinica 36 (1), 1907010-0 (2020). (Review)

13. F. A. Baltoumas#, E. Karatzas, S. Liu, S. Ovchinnikov, Y. Sofianatos, I.M. Chen, N. C. Kyrpides, G. A. Pavlopoulos#. NMPFamsDB: a database of novel protein families from microbial metagenomes and metatranscriptomes. Nucleic Acids Res. 52 (D1), D502-D512 (2024).

14. H. Wang, S. Feng, K. Tsuboyama, S. Liu, G.J. Rocklin, S. Ovchinnikov#. Disentanglement of Evolutionary Constraints in Statistical Models of Proteins. PRX Life 2 (2), 023005 (2024).

15. J. Zhang#, S. Liu, M. Chen, H. Chu, M. Wang, Z. Wang, J. Yu, N. Ni, F. Yu, D. Chen, Y. I. Yang, B. Xue, L. Yang, Y. Liu, Y. Q. Gao#. Unsupervisedly prompting AlphaFold2 for accurate few-shot protein structure prediction. J. Chem. Theory Comput. 19 (22), 8460-8471 (2023).

16. C. Norn*, B. I. M. Wicky*, D. Juergens, S. Liu, D. Kim, D. Tischer, B. Koepnick, I. Anishchenko, Foldit Players, D. Baker#, and S. Ovchinnikov#. Protein sequence design by conformational landscape optimization. Proc. Natl. Acad. Sci. U. S. A.118 (11) e2017228118 (2021)

17. Y. Xue, Y. Yang, H. Tian, H. Quan, S. Liu, L. Zhang, L. Yang, H. Zhu, H. Wu, and Y. Q. Gao#. Computational characterization of domain-segregated 3D chromatin structure and segmented DNA methylation status in carcinogenesis. Mol. Oncol. (2021)

18. H. Tian, Y. Yang, S. Liu, H. Quan, Y.Q. Gao#. Toward an understanding of the relation between gene regulation and 3D genome organization. Quant. Biol. 8, 295 (2020)

19. H. Quan, Y. Yang, S. Liu, H. Tian, Y. Xue, Y. Q. Gao#. Chromatin structure changes during various processes from a DNA sequence view. Curr. Opin. Struct. Biol. 62, 1 (2020) (Review)

20. L. Zhang*, W. J. Xie*, S. Liu, L. Meng, C. Gu and Y. Q. Gao#. DNA methylation landscape reflects the spatial organization of chromatin in different cells. Biophys. J. 113, 1395 (2017)

21. J. Zhang*, Z. Zhang*, Y. I. Yang, S. Liu, L. Yang, and Y. Q. Gao. Rich dynamics underlying solution reactions revealed by sampling and data mining of reactive trajectories. ACS Cent. Sci. 3, 407 (2017)