
电子邮件: qshao@simm.ac.cn
通信地址: 中科院上海药物所,张江祖冲之路555号
邮政编码: 201203
研究领域
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。
招生信息
招生专业
教育背景
工作经历
工作简历
发表论文
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.
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于玉琪 博士研究生 1007Z1-药物设计学