1. 以超长时间尺度分子动力学为手段探索蛋白质架构动力学，专注于蛋白质激酶和小G蛋白等信号蛋白的研究

2. 以首创的Swimming 方法研究蛋白质-小分子和蛋白质-蛋白质结合并对功能性复合蛋白大结构进行创模

3. 以分子动力学和其他计算方法推进药物研发，尤其是难成药靶点的药物研发

Swimming 模拟方法:

2011年：首创Swimming模拟方法，以物理的方法在原子水平准确模拟蛋白质与药物分子的结合过程 《JACS》

2020年：预测EGF受体激酶与癌症药物奥希替尼结合的结构，揭示原有晶体结构的不准确性 《Journal of Medicinal Chemistry》

2022年：以Swimming 方法首次准确模拟小分子药物与不可成药靶点的结合过程 《PLOS Computational Biology》

2023年：以Swimming 方法首次准确模拟靶点蛋白在与小分子药物结合过程中的大尺度架构变化《Nature Communication》

预测蛋白质-蛋白质复合结构

2013年：对EGF受体进行全尺度建模，揭示EGFR跨膜信号传导的结构机理 《Cell》

2014年：对JAK2激酶的多结构域复合结构建模，模型预测为后续晶体结构所证实 《Nature Structure & Molecular Biology》

2015年：创立EGF受体的多聚体的全尺度模型 《Nature Communication》

2021年：预测Ras-Raf 大复合信号体的结构和功能特性《Nature Structure & Molecular Biology》

蛋白质架构动力学

2012年：揭示EGF受体激酶肺癌变异导致EGFR功能失常的分子机制，这是《Cell》首次发表以计算模拟为主的工作

2009年：揭示质子化调控的架构动力学循环在激酶反应周期的核心作用 《PNAS》

2013年：揭示激酶转入无活性架构的分子过程《PNAS》

2015年：揭示协调激酶架构动力学的别构网络 《Nature Communication》

Supercomputer Algorithm Design

Shan Y.B.*, Klepeis J.L., Eastwood M.P., Dror R.O., Shaw D.E., Gaussian split Ewald: A fast Ewald mesh method for molecular simulation, https://doi.org/10.1063/1.1839571, J. Chem. Phys., February 2005

Swimming Simulations:

Shan Y.B., Kim E., Eastwood M.P., Seeliger M.A., Shaw D.E., How does a drug molecule find it target binding site, https://doi.org/10.1021/ja202726y, Journal of the American Chemical Society, May 2011

Ayaz, P., Lyczek, A., Paung, Y.T. , Mingione, V.R., Iacob, I.E., Engen. J.R., Seeliger, M.A., Shan, Y.B.*, Shaw D.E.*, Structural mechanism of a drug-binding process involving a large conformational change of the protein target, https://doi.org/10.1038/s41467-023-36956-5, Nature Communications, April 2023

Shan, Y. B.*, Mysore, V. P., Leffler, A. E., Kim, E. T., Sagawa, S., Shaw, D. E.*, How does a small molecule bind at a cryptic binding site, https://doi.org/10.1371/journal.pcbi.1009817, PLoS Computational Biology, March 2022

Yan, X.E.#, Ayaz, P.#, Zhu, S. J., Zhao, P., Liang, L., Zhang, C. H., Shan, Y. B.*, Yun, C. H.*, Structural basis of AZD9291 selectivity for EGFR T790M, https://doi.org/10.1021/acs.jmedchem.0c00891, Journal of Medicinal Chemistry, July 2020

Protein Conformational Dynamics 

Shan Y.B.*, Seeliger M.A., Eastwood, M.P., Frank F., Xu H.F., Jensen M.Ø, Dror R.O., Kuriyan J., Shaw D.E.*, A conserved protonation-dependent switch controls drug binding in the Abl kinase, https://doi.org/10.1073/pnas.0811223106, Proceedings of the National Academy of Sciences , Janurary 2009

Shan Y.B.*, Eastwood M.P., Kim E., Zhang X.W., Jumper J., Kuriyan J., Shaw D.E.*, Oncogenic Mutations Counteract Intrinsic Disorder in the EGFR Kinase and Promote Receptor Dimerization, https://doi.org/10.1016/j.cell.2012.02.063, Cell, May 2012

Shan Y.B.*, Arkhipov A., Kim E.T., Pan A.C., Shaw D.E.*, Transitions to catalytically inactive conformations in EGFR kinase, https://doi.org/10.1073/pnas.1220843110, Proceedings of the National Academy of Sciences, April 2013

Predictive Models of Large Protein Complex Structures 

Arkhipov A., Shan Y.B.*, Das R., Endres N.F., Eastwood M.P., Wemmer D.E., Kuriyan J., Shaw D.E.*, Architecture and membrane interactions of the EGF receptor, https://doi.org/10.1016/j.cell.2012.12.030, Cell, Janurary 2013

Shan Y.B.*, Gnanasambandan K., Ungureanu D., Kim E.T., Hammarén H., Yamashita K., Silvennoinen O., Shaw D.E.*, Hubbard S.R*, Molecular basis for pseudokinase-dependent autoinhibition of JAK2 tyrosine kinase, https://doi.org/10.1038/nsmb.2849, Nature Structural & Molecular Biology, June 2014

Mysore, V.P.#, Zhou, Z.W.#, Ambrogio, C.#, Li, L., Kapp, J.N., Lu, C., Shan Y.B.*, Shaw, D.E.*, A structural model of a Ras–Raf signalosome, https://doi.org/10.1038/s41594-021-00667-6, Nature Structural & Molecular Biology, October 2021