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中文摘要：
本研究群体是在多年的合作过程中自然形成，由6位科学院百人计划引进人才组成，其中国家杰出青年基金获得者3人，973计划首席科学家1人。研究群体在国内率先开展基于超级计算机和高性能计算的受体结构与功能关系研究以及药物发现研究，发展了系统化的药物设计、分子模拟和靶标发现新方法，建立了计算化学、有机合成、分子和细胞生物学紧密结合的多学科交叉创新药物研究模式，在复杂生物大分子结构与功能关系动力学模拟、药物先导化合物发现、药物作用机理研究和药物新靶标发现等多个方向均取得了优异的成绩。近5年来，在PNAS、JACS等国际SCI刊物上以通讯作者身份发表研究论文178篇(总影响因子达556)，邀请综述8篇，专著章节12篇，研究论文被他人引用729次；申请发明专利60项，实现技术转让2项。研究群体拟继续开展"药物作用新靶标、新机制和新分子实体发现方法与应用研究"，力争作出有较大影响的源头创新成果。
英文摘要：
targets identification；drug design；chemical synthesis；bioassay；mechanism of drug action
结论摘要：
本创新研究群体由6位研究人员组成，其中有国家重点基础研究发展规划(973)项目首席科学家1人，国家杰出青年基金获得者4人，中科院“百人计划人才引进基金”获得者6人。通过3年努力，研究团队形成了良好的梯队结构，事业心强、富有创新精神。研究群体建立了“靶标发现？理论计算？药物设计？化学合成(植物提取)？生物测试？药物作用机制研究”的现代创新药物研究模式，形成了计算化学/计算生物学、合成化学、植物化学、分子/细胞生物学多学科紧密协作的机制和体系，营造了良好的合作研究氛围，在创新药物基础研究和应用基础研究的多个方向均取得了优异的成绩，达到了创新群体建设的预期目标。具体成果总结如下？ 本创新研究群体改变了以往PI制单一课题组研究的方式，以项目为牵引，各课题组形成合力，联合攻关。6个课题组分工协助，发展了一系列靶标发现、药物设计和有机合成新方法，集成计算化学/计算生物学、化学(包括有机合成和植物化学)、分子细胞生物学、生物物理等技术，建立了靶标发现、药物作用机制研究和药物设计一体化的创新药物研究技术平台，形成理论计算、化学合成(植物提取)和生物测试相结合的合作研究模式。？ 综合应用上述发展的方法和技术以及建立的技术平台，本创新群体共发现药物作用新靶标10余个，特别是在利用现有药物和天然产物为探针发现新靶标方面做了较有新意的工作。？ 综合应用计算生物学、分子和细胞生物学、结构生物学方法，研究了离子通道等一系列药物靶标的结构和功能的关系。特别是在用理论计算和实验验证相结合策略研究生物大分子功能方面做出了有特色的工作。？ 针对阿尔茨海默病、肿瘤、2型糖尿病等疾病的20个靶标系统，筛选了3万余次，得到各类活性化合物400余个。？ 在Angewandte Chemie International Edition、JACS、PNAS、Cell Research、Nucleic Acids Research、Advanced Synthesis & Catalysis、Chemistry: A European Journal、Journal of Medicinal Chemistry、Green Chemistry、Organic Letters、Journal of Biological Chemistry等杂志上发表学术论文124篇，申请专利和软件著作版权30项
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期刊论文
The high affinity of hydroxamate-based MMP-12 inhibitors is due to an inherently slow dissociation o
Identification of Benzofuran-3-yl(phenyl)methanones as Novel SIRT1 Inhibitors: Binding Mode, Inhibit
The Nature and Magnitude of Specific Halogen Bonds between Iodo-perfluorobenzene and Heterocyclic Sy
Structure and Cytotoxicity of Phidianidines A and B: First Finding of 1,2,4-Oxadiazole System in a M
Palmarumycins BG1-BG7 and Preussomerin BG1: Establishment of Their Absolute Configurations Using The
Lewis Acid-Promoted Highly Diastereoselective Petasis Borono-Mannich Reaction: Efficient Synthesis o
Highly Diastereoselective Friedel-Crafts Reaction of Arenes with N-tert-Butanesulfinylimino Ester to
Design of Chiral Sulfoxide-Olefins as a New Class of Sulfur-Based Olefin Ligands for Asymmetric Cata
Design of N-Sulfinyl Homoallylic Amines as Novel Sulfinamide-Olefin Hybrid Ligands for Asymmetric Ca
A Theoretical Model for Calculating Voltage Sensitivity of Ion Channels and the Application on Kv1.2
Silver- and Gold-Mediated Domino Transformation: A Strategy for SynthesizingBenzo[e]indolo[1,2-a]pyr
Enantioselective Synthesis of Chiral 3-Aryl-1-indanones through Rhodium-Catalyzed Asymmetric Intramo
Helix unfolding/refolding characterizes the functional dynamics of Staphylococcus aureus Clp proteas
Paracaseolide A, First r-Alkylbutenolide Dimer with an Unusual Tetraquinane Oxa-Cage Bislactone Skel
Chiral Sulfinamide-Olefin Ligands: Switchable Selectivity in Rhodium-Catalyzed Asymmetric 1,2-Additi
Design and Synthesis of Polymeric Chiral Bicyclo[3.3.0] Diene as Reusable Ligand for Rhodium-Catalyz
Zn-Mediated Asymmetic Allylation of N-tert-Butanesulfinyl Ketimines: An Efficient and Practical Acce
Lewis Acid-Catalyzed Intramolecular Aza-Friedel-Crafts Reaction of N-tert-Butanesulfinyl Imines: Eff
Asymmetric Michael Addition of N-tert-Butanesulfinyl Imidates: an Efficient Strategy for the Synthes
Discovery of potent small molecule inhibitors of DYRK1A by structure-based virtual screening and bio
Structures and Absolute Stereochemistries of Nortriterpenoids from Schisandra chinensis (Turcz.) Bai
Synthesis and Biological Evaluation of 21-Arylidenepregnenolone Derivatives as Neuroprotective Agent
Utilization of Halogen Bond in Lead Optimization: A Case Study of Rational Design of Potent Phosphod
The stabilization effect of dielectric constant and acidic amino acids on arginine-arginine (Arg-Arg
Discovery and mechanism study of SIRT1 activators that promote the deacetylation of fluorophore-labe
Dongxiang Liu*. Identification of benzofuran-3-yl(phenyl)methanones as novel SIRT1 inhibitors: bindi
Unprecedented Diterpenoids as a PTP1B Inhibitor from the Hainan Soft Coral Sarcophyton trocheliophor
Asymmetric One-Pot Sequential Mannich/Hydroamination Reaction by Organo- and Gold Catalysts: Synthes
Structure-Based Design, Synthesis of C-1 and C-4 modified analogs of zanamivir as neuraminidase inhi
Flexibility of the Flap in the Active Site of BACE1 as Revealed by Crystal Structures and MD Simulat
M. Ammonium transport proteins with changes in one of the conserved pore histidines have different p
Backdoor opening mechanism in acetylcholinesterase based on X-ray crystallography and molecular dyna
Structure and Synthesis of a Unique Isonitrile Lipid Isolated from the Marine Mollusk Actinocyclus p
Structural and functional characterization of the interaction of the photosensitizing probe methylen
Identification of Pentacyclic Triterpenes Derivatives as Potent Inhibitors against Glycogen Phosphor
The gating charge pathway of an epilepsy-associated potassium channel accommodates chemical ligands.
Rhodium-Catalyzed Highly Enantioselective Addition of Arylboronic Acids to Cyclic Aldimines: Practic
Aquantum mechanics/molecular mechanics study on the hydrolysis mechamism of New Delhi metallo-B-lact
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