GPCR-AI 发现平台
从受体机制研究走向候选药物。
以分子机制为起点，将结构研究、计算设计、人工智能与功能实验连接成快速迭代的研发体系。
02 / 06
平台逻辑
让计算预测与实验验证在每轮设计中相互校正。
AI 并非孤立的工具，而是贯穿 GPCR 机制研究、结构解析、分子生成、虚拟筛选、性质优化和功能检测的研发方法。每轮实验结果都会成为下一轮设计的依据。
UNDERSTANDDESIGNTEST
01研究领域 01
GPCR 分子机制研究
膜蛋白
G 蛋白偶联受体（GPCR）是最重要的药物靶点类别之一，约四成已上市药物通过 GPCR 发挥作用。深入理解受体结构、动态构象与信号转导机制，是开展理性药物设计的重要基础。
AlphaMol
团队长期研究受体介导的信号转导，在 Cell、Nature、Nature Communications、Chemical Science、Trends in Biochemical Sciences 和 Angewandte Chemie 等期刊发表了多项相关成果。
相关论文18 篇研究成果
Functional dynamics of G protein-coupled receptors reveal new routes for drug discoveryNature Reviews Drug Discovery
The structure and function of olfactory receptorsTrends in Pharm Sci
Molecular basis of ligand selectivity for melatonin receptorsRSC Adv
The role of metal ions in GPCR signaling and drug discoveryComputational Molecular Science
Structural basis of CXC chemokine receptor 2 activation and signallingNature
Activation and Signaling Mechanism Revealed by Cannabinoid Receptor-Gi Complex StructuresCell
Enhancing the Signaling of GPCRs via Orthosteric IonsACS Central Science
New binding sites, new opportunities for GPCR drug discoveryTrends in Biochemical Sciences
New binding sites, new opportunities for GPCR drug discoveryTrends in Biochemical Sciences
Exploring a new ligand binding site of G protein-coupled receptorsChemical Science
5-HT2C Receptor Structures Reveal the Structural Basis of GPCR PolypharmacologyCell
Designing Safer Analgesics via µ-Opioid Receptor PathwaysTrends in Pharmacological Sciences
The Molecular Mechanism of P2Y1 Receptor ActivationAngewandte Chemie Int Ed Engl
Mechanistic Studies on the Stereoselectivity of the Serotonin 5-HT1A ReceptorAngewandte Chemie Int Ed Engl
The Mechanism of Ligand-Induced Activation or Inhibition of mu- and kappa-Opioid ReceptorsAngewandte Chemie Int Ed Engl
W246 Opens a Gate for a Continuous Intrinsic Water Pathway during Activation of the Adenosine A ReceptorAngewandte Chemie Int Ed Engl
Activation of G-protein-coupled receptors correlates with the formation of a continuous internal water pathwayNature Communications
Advances in GPCR modeling evaluated by the GPCR Dock 2013 assessment: meeting new challengesStructure
02研究领域 02
GPCR 功能检测技术
G蛋白偶联受体
GPCR 位于细胞膜上，其功能检测长期面临信号间接、动力学信息不足和通路分辨率有限等挑战。AlphaMol 重点解决以下问题：
(1) 在无标记条件下检测药物活性；
(2) 直接测量 GPCR 与 G 蛋白的相互作用；
(3) 获取药物分子的结合与解离动力学；
(4) 区分不同 G 蛋白亚型介导的信号。
(1) 在无标记条件下检测药物活性；
(2) 直接测量 GPCR 与 G 蛋白的相互作用；
(3) 获取药物分子的结合与解离动力学；
(4) 区分不同 G 蛋白亚型介导的信号。
团队开发了一系列生物芯片与功能检测技术，用于提高 GPCR 药理数据的准确性、信息量与实验效率，为分子设计提供更直接的反馈。
相关论文4 篇研究成果
Single-vesicle assays using liposomes and cell-derived vesicles: from modeling complex membrane processes to synthetic biology and biomedical applicationsChemical reviews
Activation of G-protein-coupled receptors in cell-derived plasma membranes supported on porous beadsJACS
Micropatterned immobilization of a G protein–coupled receptor and direct detection of G protein activationNature Biotechnology
Incorporation of Rhodopsin in Laterally Structured Supported Membranes: Observation of Transducin Activation with Spatially and Time-Resolved Surface Plasmon Resonance†Biochemistry
03研究领域 03
计算与 AI 药物设计
AlphaMol
AlphaMol 构建了面向 GPCR 的计算与 AI 药物设计平台，覆盖靶点研究、结构预测、分子生成、虚拟筛选、先导化合物优化、分子模拟、性质预测和结合能评估等环节。
平台与药物化学及功能实验紧密衔接，以实验数据持续修正模型和设计策略，从而更高效地获得具有活性、选择性与可开发性的候选分子。
平台与药物化学及功能实验紧密衔接，以实验数据持续修正模型和设计策略，从而更高效地获得具有活性、选择性与可开发性的候选分子。
相关论文17 篇研究成果
Enhancing Multifunctional Drug Screening via Artificial IntelligenceDigital Discovery
Identifying Potent Compounds Using Pairwise Consensus MethodsJournal of Chemical Information and Modeling
Rational Design Biased Compounds against μ-Opioid ReceptorACS Pharmacology & Translational Science
Functional dynamics of G protein-coupled receptors reveal new routes for drug discoveryNature Reviews Drug Discovery
Computational drug development for membrane protein targetsNature Biotechnology
Will the hype of automated drug discovery finally be realized?Expert Opinion on Drug Discovery
Celastrol Combats Methicillin-Resistant Staphylococcus aureus by Targeting Δ1-Pyrroline-5-Carboxylate DehydrogenaseAdvanced Science
Rutin, a Natural Inhibitor of IGPD Protein, Inhibits the Formation of Biofilm in Staphylococcus xylosus ATCC700404 in vitro and in vivoFrontiers in Pharmacology
MolADI: A Web Server for Automatic Analysis of Protein–Small Molecule Dynamic InteractionsMolecules
Clinical HDAC Inhibitors are Effective Drugs to Prevent the Entry of SARS-CoV2ACS Pharmacology & Translational Science
Enhancing the Signaling of GPCRs via Orthosteric IonsACS Central Science
Advancing Drug Discovery via Artificial IntelligenceTrends in Pharmacological Sciences
Computational modeling of the olfactory receptor Olfr73 suggests a molecular basis for low potency of olfactory receptor-activating compoundsCommunications Biology
New binding sites, new opportunities for GPCR drug discoveryTrends in Biochemical Sciences
Exploring a new ligand binding site of G protein-coupled receptorsChemical Science
Implementing WebGL and HTML5 in Macromolecular Visualization and Modern Computer-Aided Drug DesignTrends in Biotechnology
Using PyMOL as a platform for computational drug designComputational Molecular Science
04研究领域 04
原生脂质环境中的膜蛋白结构
膜蛋白
GPCR、离子通道和转运蛋白等膜蛋白是重要的药物靶点。传统结构研究常在去垢剂或人工脂质体系中进行，可能难以完整保留膜蛋白在生理环境中的构象与功能状态。
AlphaMol
团队正在建立更接近原生脂质环境的膜蛋白结构研究流程，并结合中国与瑞士的冷冻电镜资源，为基于结构的药物设计提供更具生理相关性的依据。
相关论文8 篇研究成果
Cryo-EM structures of ClC-2 chloride channel reveal the blocking mechanism of its specific inhibitor AK-42Nat Commun
Cryo-EM structure of human heptameric pannexin 2 channelNature Communications
Asymmetric opening of the homopentameric 5-HT3A serotonin receptor in lipid bilayersNature Communications
A Gating Mechanism of the Serotonin 5-HT3 ReceptorStructure
The Structure of the Mouse Serotonin 5-HT3 Receptor in Lipid VesiclesStructure
X-ray structure of the mouse serotonin 5-HT3 receptorNature
Molecular and dimensional profiling of highly purified extracellular vesicles by fluorescence fluctuation spectroscopyAnalytical Chemistry
Overcoming barriers to membrane protein structure determinationNature Biotechnology
05研究领域 05
生物计算与算法创新
AlphaMol
先导化合物优化需要在活性、选择性、理化性质、安全性和可开发性之间取得平衡。AlphaMol 围绕这一过程开发结合能预测、分子性质预测和成药性评估等计算方法。
其中，AlphaE 用于评估化合物结合活性，并针对较大结构变化、不同结合口袋和计算资源消耗等常见问题进行方法优化。相关算法与实验数据协同使用，为药物化学决策提供量化依据。
其中，AlphaE 用于评估化合物结合活性，并针对较大结构变化、不同结合口袋和计算资源消耗等常见问题进行方法优化。相关算法与实验数据协同使用，为药物化学决策提供量化依据。
相关论文6 篇研究成果
Machine learning deciphered molecular mechanistics with accurate kinetic and thermodynamic predictionJournal of Chemical Theory and Computation
Accurate Physical Property Predictions via Deep LearningMolecules
MolADI: A Web Server for Automatic Analysis of Protein–Small Molecule Dynamic InteractionsMolecules
Advancing Drug Discovery via Artificial IntelligenceTrends in Pharmacological Sciences
Implementing WebGL and HTML5 in macromolecular visualization and modern computer-aided drug designTrends in Biotechnology
Using PyMOL as a platform for computational drug designComputational Molecular Science
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