1. 计算机辅助药物设计、人工智能方法的开发及应用

计算机辅助药物设计在新药研发中发挥着不可或缺的作用，但准确性受到诸多因素的制约。前期，我们开发了优化的分子力场和量化计算方法提升靶标蛋白-药物的结合亲和力预测水平；开发了一系列增强采样的分子模拟方法实现对蛋白质结构动态的高效扫描,应用于药物分子的高通量筛选。目前，我们进一步开发人工智能AI驱导的分子模拟、量化算法以及基于机器学习的蛋白-药物结合模式及相互作用的预测模型，提高药物筛选、发现与设计的准确性。针对多种疾病靶点开展基于结构的药物设计研究。

 

2. AI 驱动的共价抑制剂研究

  生物体系中的复杂反应（如酶催化反应）很难用实验手段进行研究，计算模拟可以评估反应涉及的过渡态、中间体的结构和能量，对反应机制提供分子层面上的理解。我们将深度学习势能整合到多尺度模拟 QM/MM 方法中，实现对酶的催化反应机制的精确解释、共价抑制剂的快速发现与设计。

 

3. 药物靶点的功能机制研究

  生物大分子发挥功能时通常伴随着构象上的变化以及蛋白-蛋白、蛋白-核酸的相互作用，无法被实验技术解析。我们将自主研发的计算方法与 alphafold3 结合，应用于生物体系的复杂动态运动以及蛋白-蛋白、蛋白-核酸的相互作用研究，通过对构象的大规模搜索以及数据分析，揭示生物体系的功能运行及疾病的发病机制，并用于药物设计。研究体系包括各种 GPCR、激酶、半胱氨酸蛋白酶、RNA 聚合酶（RdRP），等等。

4. 酶的设计改造以及蛋白、多肽（包括环肽）的从头设计研究

  我们采用 AI 及生物信息学方法对酶进行设计改造，实现对酶的热稳定性和催化活性的大幅提升。此外，采用 Diffusion 生成模型以及蛋白质设计软件 ROSETTA 设计优化蛋白序列，经由alphafold3 以及分子模拟对序列筛选，最后通过实验验证设计靶向抗病毒靶点的蛋白质、多肽药物。

   

1007Z1-药物设计学

2004-08--2009-12   TexasA&M University, Texas, USA   博士
2003-08--2004-05   College of William & Mary, Virginia, USA   硕士
1999-09--2003-06   南京大学化学与化工学院   研究生毕业
1995-09--1999-06   南京大学化学与化工学院   学士

   

2020-10~现在, 中科院上海药物研究所, 研究员
2011-10~2020-10,中科院上海药物研究所, 副研究员
2010-01~2011-09,北京大学化学与分子工程学院, 博士后

2025年

1. H. Su#, G. Wu#, M. Xiong#, Y. Wang#, J. Cao#, M. You, Y. Xiang, T. Nie, M. Li, G. Xiao, L. Zhang*, Q. Shao*, Y. Xu*. Dynamic cap-mediated substrate access and potent inhibitor design of monkeypox virus I7L protease. Adv. Sci. 2025, DOI: 10.1002/advs.202501625.

2024年

1. M. Xiong#, T. Nie#, Z. Li, M. Hu, H. Su, H. Hu, Y. Xu*, Q. Shao*. Potency prediction of covalent inhibitors against SARS-CoV-2 3CL-like protease and multiple mutants by multiscale simulations. J. Chem. Inf. Model. 2024, DOI: 10.1021/acs.jcim.4c01594.

2023年

1.     X. Wang^#, M. Wang^#, T. Xu^#, Y. Feng^#, Q. Shao^#, S. Han, X. Chu, Y. Xu, S. Lin*, Q. Zhao*, B. Wu*. Structural insights into dimerization and activation of the mGlu2–mGlu3 and mGlu2–mGlu4 heterodimers. Cell Res. 2023, 33: 762–774.

2.     Q. Shao*, M. Xiong, J. Li, H. Hu, H. Sua, Y. Xu*. Unraveling the catalytic mechanism of SARS-CoV-2 papain-like protease with allosteric modulation of C270 mutation using multiscale computational approaches. Chem. Sci. 2023, 14: 4681. 

2022年

1. Muya Xiong¹, Tianqing Nie¹, Qiang Shao, Minjun Li, Haixia Su, Yechun Xu^*. In silico screening-based discovery of novel covalent inhibitors of the SARS-CoV-2 3CL protease, Eur. J. Med. Chem. 2022, 231：114130.  

2. Hangchen Hu, Qian Wang, Haixia Su, Qiang Shao, Wenfeng Zhao, Guofeng Chen, Minjun Li^*, Yechun Xu^*. Identification of Cysteine 270 as a Novel Site for Allosteric Modulators of SARS-CoV-2 Papain-Like Protease, Angew. Chem. Int. Ed. Engl. 2022, 61: e202212378.

2021年

1. Su, Haixia¹; Yao, Sheng¹; Zhao, Wenfeng¹; Zhang, Yuming¹; Liu, Jia¹; Shao, Qiang¹; Wang, Qingxing; Li, Minjun; Xie, Hang; Shang, Weijuan; Ke, Changqiang; Feng, Lu; Jiang, Xiangrui; Shen, Jingshan;Xiao, Gengfu; Jiang, Hualiang; Zhang, Leike*; Ye, Yang*; Xu,Yechun*. Identification of pyrogallol as a warhead in design of covalent inhibitors for the SARS-CoV-2 3CL protease, Nat. Commun. 2021, 12：3623.  

2. Xiong, Muya; Su, Haixia; Zhao, Wenfeng; Xie, Hang; Shao, Qiang^*; Xu, Yechun^*. What coronavirus3C‐like protease tellsus: From structure, substrate selectivity, to inhibitor design, Med. Res. Rev. 2021,41：1965-1998. 

3. Hui Zhang¹, Kun Chen¹, Qiuxiang Tan¹, Qiang Shao¹, Shuo Han¹, Chenhui Zhang, Cuiying Yi, Xiaojing Chu, Ya Zhu*, Yechun Xu^*, Qiang Zhao^*, Beili Wu^*. Structural basis for chemokine recognition and receptor activation of chemokine receptor CCR5. Nat. Commun. 2021, 12: 4151. 

2019年

1. Qiang Shao*, Weiliang Zhu. Ligand binding effects on the activation of EGFR extracellular domain. Phys. Chem. Chem. Phys. 2019, 21, 8141-8151. (*通讯作者)

2. Qiang Shao*, Weiliang Zhu. Nonnative Contact Effects in Protein Folding. Phys. Chem. Chem. Phys. 2019, 21, 11924-11936.

3. Qiang Shao*, Weiliang Zhu. Selective enhanced sampling in dihedral energy facilitates overcoming the dihedral energy increase in protein folding and accelerates the searching for protein native structure. Phys. Chem. Chem. Phys. 2019, 21, 10423-10435.

4. Qiang Shao*, Weiliang Zhu. Exploring the Ligand Binding/Unbinding Pathway by Selectively Enhanced Sampling of Ligand in a Protein−Ligand Complex. J. Phys. Chem. B 2019, 123, 7974-7983.

2018年

1. Qiang Shao*, Weiliang Zhu. Assessing AMBER force fields for protein folding in an implicit solvent. Phys. Chem. Chem. Phys. 2018, 20, 7206-7216. 

2. Qiang Shao*, Weiliang Zhu. The effects of implicit modeling of nonpolar solvation on protein folding simulation. Phys. Chem. Chem. Phys. 2018, DOI: 10.1039/C8CP03156H.

2017年

1. Qiang Shao*, Weiliang Zhu. Effective conformational sampling in explicit solvent with Gaussian biased accelerated molecular dynamics. J. Chem. Theory Comput. 2017, 13: 4240-4252.

2. Qiang Shao*, Weiliang Zhu. How well can implicit solvent simulations explore folding pathways? A quantitative analysis of α-helix bundle proteins. J. Chem. Theory Comput. 2017, 13: 6177-6190.

3. Qiang Shao*, Jiye Shi*, Weiliang Zhu. Determining protein folding pathway and associated energetics through partitioned integrated-tempering-sampling simulation. J. Chem. Theory Comput. 2017, 13: 1229-1243.

4.  Qiang Shao*, Zhijian Xu, Jinan Wang, Jiye Shi*, Weiliang Zhu. Energetics and structural characterization of the ‘‘DFG-flip’’ conformational transition of B-RAF kinase: A SITS molecular dynamics study. Phys. Chem. Chem. Phys. 2017, 19: 1257-1267.

5. Yuqi Yu, Jinan Wang, Zhaoqiang Chen, Guimin Wang, Qiang Shao*, Jiye Shi*, Weiliang Zhu*. Structural insights into HIV-1 protease flap opening processes and key intermediates. RSC Adv. 2017, 7: 45121-45128.

2016年

1. Qiang Shao*. Enhanced conformational sampling technique provides an energy landscape view of large-scale protein conformational transitions. Phys. Chem. Chem. Phys. 2016, 18: 29170-29182.

2. Yuqi Yu, Jinan Wang, Qiang Shao*, Jiye Shi*, Weiliang Zhu*. The effects of organic solvents on the folding pathway and associated thermodynamics of proteins: A microscopic view. Sci. Rep. 2016, 6: 19500.

3. Jinan Wang, Qiang Shao*, Benjamin Crossins, Jiye Shi*, Kaixian Chen, Weiliang Zhu*. Thermodynamics calculation of protein-ligand interactions by QM/MM polarizable charge parameters. J. Biomol. Struct. Dyn. 2016, 34: 163.

4. Jing Li1, Jose Pindado Rodriguez1, Fengfeng Niu, Mengchen Pu, Jinan Wang, Li-Wei Hung, Qiang Shao, Yanping Zhu, Wei Ding, Yanqing Liu, Yurong Da, Zhi Yao, Jie Yang, Yongfang Zhao, Gong-Hong Wei, Genhong Cheng, Zhi-Jie Liu, Songying Ouyang*. Structural basis for DNA recognition by STAT6. Proc. Natl. Acad. Sci. USA 2016, 113: 13015-13020.

5. Zhaoqiang Chen，Guimin Wang, Zhijian Xu*, Jinan Wang, Yuqi Yu, Tingting Cai, Qiang Shao, Jiye Shi*, Weiliang Zhu*. How do distance and solvent affect halogen bonding involving negatively charged donors? J. Phys. Chem. B 2016, 120: 8784-8793.

2015年

1. Yang Lijiang, Liu Chengwen, Shao Qiang, Zhang Jun, Gao Yi Qin*. From thermodynamics to kinetics: enhanced sampling of rare events. Acc. Chem. Res. 2015, 48:947-955
2. Yu Yuqi, Wang Jinan, Shao Qiang*, Shi Jiye*, Zhu Weiliang*. Effects of drug-resistant mutations on the dynamic properties of HIV-1 protease and inhibition by Amprenavir and Darunavir. Sci. Rep. 2015, 5:10517.
3. Yu Yuqi, Wang Jinan, Shao Qiang*, Shi Jiye*, Zhu Weiliang*. Increasing the sampling efficiency of protein conformational transition using velocity-scaling optimized hybrid explicit/implicit solvent REMD simulation. J. Chem. Phys. 2015, 142, 125105.
4. Wang Jinan, Shao Qiang*, Crossins Benjamin, Shi Jiye*, Chen Kaixian, Zhu Weiliang*. Thermodynamics calculation of protein-ligand interactions by QM/MM polarizable charge parameters. J. Biomol. Struct. Dyn.2015, accepted
5. Shao Qiang*. Folding or misfolding: The choice of β‑hairpin. J. Phys. Chem. B 2015, 119:3893-3900.
6. Shao Qiang*. Important roles of hydrophobic interactions in folding and charge interactions in misfolding of α-helix bundle protein. ASC Adv. 2015, 5, 4191-4199.
7. Xiong Xiuming, Chen Zhaoqiang, Cossins Benjamin, Xu Zhijian, Shao Qiang, Ding K., Zhu Weiliang*, Shi Jiye*. Force fields and scoring functions for carbohydrate simulation. Carbohydr. Res. 2015, 401:73-81.

2014年
1. Wang Jinan, Shao Qiang*, Xu Zhijian, Liu Yingtao, Yang Zhuo, Cossins Benjamin, Jiang Hualiang, Chen Kaixian, Shi Jiye*, Zhu Weiliang*. Exploring transition pathway and free energy profile of large-scale protein conformational change by combining normal mode analysis and umbrella sampling molecular dynamics. J. Phys. Chem. B 2014, 118: 134-143.
2. Wang Jinan, Peng Shaoliang, Cossins Benjamin, Liao Xiangke, Chen Kaixian, Shao Qiang*, Zhu X*, Shi Jiye*, Zhu Weiliang. Mapping central α-helix linker mediated conformational transition pathway of calmodulin via simple computational approach. J. Phys. Chem. B 2014, 118, 9677-9685.
3. Shao Qiang*, Wang Jinan, Zhu Weiliang. On the influence of the mixture of denaturants on protein structure stability: A molecular dynamics study.  Chem. Phys. 2014, 441, 38-46.
4. Shao Qiang*. Probing sequence dependence of folding pathway of α-helix bundle proteins through free energy landscape analysis. J. Phys. Chem. B 2014, 118: 5891-5900.
5.Shao Qiang*. Methanol concentration dependent protein denaturing ability of guanidinium/methanol mixed solution. J. Phys. Chem. B 2014, 118: 6175-6185.
6.Shao Qiang*. The addition of 2,2,2-trifluoroethanol prevents the aggregation of guanidinium around protein and impairs its denaturation ability: A molecular dynamics simulation study. Proteins,2014, 82: 944-953.

2013年
1. Shao Qiang*, Wang Jinan, Shi Jiye, Zhu Weiliang. The universality of β-hairpin misfolding indicated by molecular dynamics simulations. J. Chem. Phys. 2013, 139: 165103/1-165103/8.
2. Shao Qiang*, Shi Jiye*, Zhu Weiliang. Molecular dynamics simulation indicating cold denaturation of β-hairpins. J. Chem. Phys. 2013, 138: 085102/1-085102/10.
3. Zhang Zhengyan, Xu Zhijian, Yang Zhuo, Liu Yingtao, Wang Jinan, Shao Qiang, Li Shujin, Lu Yunxiang, Zhu Weiliang.* The stabilization effect of dielectric constant and acidic amino acids on arginine-arginine (Arg-Arg) pairings: Database survey and computational studies. J. Phys. Chem. B, 2013, 117: 4827-4835. 
4.  Wu Tianmin, Yang Lijiang, Zhang Ruiting, Shao Qiang, Zhuang Wei.* Modeling the thermal unfolding 2DIR spectra of a β-hairpin peptide based on the implicit solvent MD simulation.  J. Phys. Chem. A, 2013, 117: 6256-6263.
5. Shao Qiang*. On the influence of hydrated imidazolium-based ionic liquid on protein structure stability: A molecular dynamics simulation study. J. Chem. Phys. 2013, 139: 115102/1-115102/8.
6. Wang Jinan, Fulford Tim, Shao Qiang, Javelle Arnaud, Yang Huaiyu, Zhu Weiliang,* Merrick Mike.* Ammonium transport proteins with changes in one of the conserved pore histidines have different performance in ammonia and methylamine conduction. Plos One 2013, 8: e62745. 

2012年
1. Shao Qiang, Zhu Weiliang, Gao Yi Qin.* Robustness in protein folding revealed by thermodynamics calculation. J. Phys. Chem. B 2012, 116: 13848-13856.
2. Shao Qiang*, Shi Jiye, Zhu Weiliang.* Enhanced sampling molecular dynamics simulation captures experimentally suggested intermediate and unfolded states in the folding pathway of Trp-cage miniprotein. J. Chem. Phys. 2012, 137: 125013/1-125013/10.
3. Shao Qiang*, Gao Yi Qin.* Water plays an important role in osmolyte-induced hairpin structure change: A molecular dynamics simulation study. J. Chem. Phys. 2012, 137: 145101/1-145101/10.
4. Shao Qiang, Fan Yubo, Yang Lijiang, Gao Yi Qin.* Counterion effects on the denaturing activity of guanidinium cation to protein. J. Chem. Theory Comput. 2012, 8: 4364-4373.
5. Shao Qiang, Fan Yubo, Yang Lijiang, Gao Yi Qin.* From protein denaturant to protectant: Comparative molecular dynamics study of alcohol/protein interactions, J. Chem. Phys. 2012, 136, 115101/1-115101/9 (封面文章, research highlights).
6. Lyu Zhi-Xin, Shao Qiang, Gao Yi Qin,* Zhao Xin Sheng.* Direct observation of the uptake of outer membrane proteins by the periplasmic chaperone Skp, Plos One 2012, 7: e46068.
7. Shao Qiang, Gao Yi Qin.* The protein folding mechanism revealed by the folding free energy landscape analysis and denaturation simulations, Curr. Phys. Chem. 2012, 2: 33-44.
8. Yang Lijiang, Shao Qiang, Gao Yi Qin.* Enhanced sampling method in molecular simulations, Prog. Chem. 2012, 24: 1199-1213.

2011年
1. Shao Qiang, Yang Lijiang, Gao Yi Qin.* Structure change of β-hairpin induced by turn optimization: An enhanced sampling molecular dynamics simulation study,J. Chem. Phys. 2011, 135: 235104/1-235104/10.
 2.Shao Qiang, Gao Yi Qin.* The relative helix and hydrogen bond stability in the B domain of protein A as revealed by ITS MD simulation, J. Chem. Phys.2011, 135: 135102/1-135102/12.
3. Hwang Soyoun1, Shao Qiang1, Williams Howard, Hilty Christian,* Gao Yi Qin.* Methanol strengthens hydrogen bonds and weakens hydrophobic interactions in proteins-A combined molecular dynamics and NMR study, J. Phys. Chem. B2011, 115: 6653-6660. (1共同一作)
4. Chen Liuxi, Shao Qiang, Gao Yi Qin, Russell H. David.* A molecular dynamics and ion mobility spectrometry study of modelβ-hairpin peptide, Trpzip1, J. Phys. Chem. A 2011, 115: 4427-4435.

2010年
1. Shao Qiang, Gao Yi Qin.* Temperature dependence of hydrogen-bond stability in β-hairpin structures, J. Chem. Theory Comput. 2010, 6: 3750-3760.
2. Shao Qiang, Wei Haiyan, Gao Yi Qin.* Effects of turn stability and side-chain hydrophobicity on the folding of β-structures, J. Mol. Biol.2010, 402: 595-609.
3. Wei Haiyan, Shao Qiang, Gao Yi Qin.* The effects of side chain hydrophobicity on the denaturation of simple β-hairpins, Phys. Chem. Chem. Phys.2010, 12: 9292-9299.
4. Lund Liliya, Fan Yubo, Shao Qiang, Gao Yi Qin,* and Raushel M. Frank.* Carbamate transport in carbamoyl phosphate synthetase: A theoretical and experimental investigation, J. Am. Chem. Soc. 2010, 132: 3870-3878.

2006~2009年
1. Gao Yi Qin,* Shao Qiang The chemomechanical coupling mechanisms of kinesin and dynein, Proteins Energy Heat & Signal Flow 2009, Book chapter.
2. Fan Yubo, Lund Liliya, Shao Qiang, Gao Yi Qin,* and Raushel M. Frank.* A combined theoretical and experimental study of the ammonia tunnel in carbamoyl phosphate synthetase,J. Am. Chem. Soc. 2009, 131:10211-10219.
3. Shao Qiang, Yang Lijiang, Gao Yi Qin.* A test of implicit solvent models on the folding simulation of the GB1 peptide, J. Chem. Phys. 2009, 130:195104/1-195104/6.
4. Yang Lijiang, Shao Qiang, Gao Yi Qin.* Thermodynamics and folding pathways of trpzip2: An accelerated molecular dynamics simulation study, J. Phys. Chem. B 2009, 113: 803-808.
5.Yang Lijiang, Shao Qiang, Gao Yi Qin.* Comparison between integrated and parallel tempering methods in enhanced sampling simulations, J. Chem. Phys. 2009, 130:124111/1-124111/8.
6. Gao Yi Qin,* Yang Lijiang, Fan Yubo, Shao Qiang. Thermodynamics and kinetics simulations of multi-time-scale processes for complex systems, Int. Rev. Phys. Chem. 2008, 27: 201-227.
7. Shao Qiang, Gao Yi Qin.* Asymmetry in kinesin walking, Biochemistry2007, 46: 9098-9106.
8. Shao Qiang, Gao Yi Qin.* On the hand-over-hand mechanism of kinesin, Proc. Natl. Acad. Sci. USA 2006, 103: 8072-8077.

   

（ 1 ） 新冠病毒蛋白酶研究：从别构位点发现到别构抑制剂设计, 负责人, 国家任务, 2025-01--2028-12
（ 2 ） ACE2重组蛋白和多肽的设计改造研究, 负责人, 国家任务, 2021-01--2024-12
（ 3 ） 膜蛋白的结构精修及功能性构象变化研究, 负责人, 研究所自主部署, 2017-06--2019-01
（ 4 ） 膜蛋白的结构精修及功能性构象变化研究, 负责人, 研究所自主部署, 2017-03--2019-03
（ 5 ） 针对EBOV、MERS-CoV、ZIKV、DENV、CHIKV造成的五种新发突发外来疫病的宿主和相关媒介的生物防控技术与产品的研发, 参与, 国家任务, 2017-01--2019-12
（ 6 ） NSFC-广东联合基金（第二期）超级计算科学应用研究, 负责人, 地方任务, 2016-02--2017-07
（ 7 ） 蛋白质大规模构象变化的模拟方法发展及应用研究, 负责人, 国家任务, 2014-01--2017-12
（ 8 ） 蛋白质复合体和膜蛋白结构生物学中的新技术和新方法研究, 参与, 国家任务, 2014-01--2018-12
（ 9 ） 重要G蛋白偶联受体的结构与功能研究及配体发现, 参与, 国家任务, 2012-01--2016-12
（ 10 ） 核糖体对新生肽链,蛋白质与蛋白质之间的相互反应对蛋白质的折叠影响的理论模拟研究, 负责人, 国家任务, 2011-01--2013-12
（ 11 ） 自组装的理论与模拟, 参与, 国家任务, 2011-01--2014-12

（1）增强取样分子模拟方法发展及在蛋白质功能运动的应用研究   第二届世界华人计算生物和分子模拟大会   2018-06-07
（2）蛋白质动态运动的增强取样分子模拟   中国化学会第31届学术年会   2018-05-04

已指导学生

于玉琪  博士研究生  1007Z1-药物设计学