Generative Active Learning for the Search of Small-molecule Protein Binders
Mila – Québec AI Institute（米拉-魁北克人工智能研究所）；Dreamfold；McGill University（麦吉尔大学）；Université de Montréal（蒙特利尔大学）；IRIC, Université de Montréal（蒙特利尔大学IRIC研究所）；Valence Labs（Valence实验室）；X-Chem（X-Chem公司）；MIT（麻省理工学院）；AI Redefined
Maksym Korablyov, Cheng-Hao Liu, Moksh Jain, Almer M. van der Sloot, Eric Jolicoeur, Edward Ruediger, Andrei Cristian Nica, Emmanuel Bengio, Kostiantyn Lapchevs… 展开作者
Maksym Korablyov, Cheng-Hao Liu, Moksh Jain, Almer M. van der Sloot, Eric Jolicoeur, Edward Ruediger, Andrei Cristian Nica, Emmanuel Bengio, Kostiantyn Lapchevskyi, Daniel St-Cyr, Doris Alexandra Schuetz, Victor Ion Butoi, Jarrid Rector-Brooks, Simon Blackburn, Leo Feng, Hadi Nekoei, SaiKrishna Gottipati, Priyesh Vijayan, Prateek Gupta, Ladislav Rampášek, Sasikanth Avancha, Pierre-Luc Bacon, William L. Hamilton, Brooks Paige, Sanchit Misra, Stanislaw Kamil Jastrzebski, Bharat Kaul, Doina Precup, José Miguel Hernández-Lobato, Marwin Segler, Michael Bronstein, Anne Marinier, Mike Tyers, Yoshua Bengio
Despite substantial progress in machine learning for scientific discovery in recent years, truly de novo design of small molecules which exhibit a property of interest remains a significant challenge. We introduce LambdaZero, a generative active learning approach to search for synthesizable molecules. Powered by deep reinforcement learning, LambdaZero learns to search over the vast space of molecules to discover candidates with a desired property. We apply LambdaZero with molecular docking to design novel small molecules that inhibit the enzyme soluble Epoxide Hydrolase 2 (sEH), while enforcing constraints on synthesizability and drug-likeliness. LambdaZero provides an exponential speedup in terms of the number of calls to the expensive molecular docking oracle, and LambdaZero de novo designed molecules reach docking scores that would otherwise require the virtual screening of a hundred billion molecules. Importantly, LambdaZero discovers novel scaffolds of synthesizable, drug-like inhibitors for sEH. In in vitro experimental validation, a series of ligands from a generated quinazoline-based scaffold were synthesized, and the lead inhibitor N-(4,6-di(pyrrolidin-1-yl)quinazolin-2-yl)-N-methylbenzamide (UM0152893) displayed sub-micromolar enzyme inhibition of sEH.
AutoBinder Agent: An MCP-Based Agent for End-to-End Protein Binder Design
Guangzhou Institutes of Biomedicine and Health（广州生物医学研究院）；Chinese Academy of Sciences（中国科学院）；Renmin University of China（中国人民大学）；South China University of Technology（华南理工大学）；RIKEN, Japan（日本理化学研究所）；Westlake University（西湖大学）
AlloGen: Conformation-Selective Binder Generation with Differential State Scoring
Department of Computer Science and Engineering（计算机科学与工程系）；The Chinese University of Hong Kong（香港中文大学）；Department of Bioengineering（生物工程系）；University of Pennsylvania（宾夕法尼亚大学）；Department of Computer and Information Science（计算机与信息科学系）
UniMoMo: Unified Generative Modeling of 3D Molecules for De Novo Binder Design
Tsinghua University（清华大学）；Institute for AI Industry Research (AIR), Tsinghua University（清华大学人工智能产业研究院）；Renmin University of China（中国人民大学）；Bytedance（字节跳动）
Designing Protein Structures from Natural Language
University of Washington（华盛顿大学）；National University of Singapore（新加坡国立大学）；Allen Institute for AI (Ai2)（艾伦人工智能研究所）；Howard Hughes Medical Institute（霍华德·休斯医学研究所）
Cross-Chirality Generalization by Axial Vectors for Hetero-Chiral Protein-Peptide Interaction Design
Department of Chemistry, Tsinghua University, Beijing, China（清华大学化学系）；School of Life Sciences, Tsinghua University, Beijing, China（清华大学生命科学学院）；Anew Labs, Shanghai, China（Anew实验室）；Tsinghua-Peking Center for Life Sciences, Beijing, China（清华大学-北京大学生命科学中心）；Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Tsinghua University, Beijing, China（教育部生物有机磷化学与化学生物学重点实验室）；Center for Synthetic and Systems Biology, Tsinghua University, Beijing, China（合成与系统生物学中心）；Beijing Frontier Research Center for Biological Structure, Tsinghua University, Beijing, China（北京生物结构前沿研究中心）；Qiuzhen College, Tsinghua University, Beijing, China（齐臻学院）；Yau Mathematical Sciences Center, Tsinghua University, Beijing, China（叶德平数学科学中心）；Institute for AI Industry Research (AIR), Tsinghua University, Beijing, China（人工智能产业研究院（AIR），清华大学）；AI Industry Research Innovation Center,Wuxi Research Institute for Applied Technologies, Tsinghua University（人工智能产业研究创新中心，无锡应用技术研究院，清华大学）
TD3B: Transition-Directed Discrete Diffusion for Allosteric Binder Generation
Department of Computer Science and Engineering, The Chinese University of Hong Kong（香港中文大学计算机科学与工程系）；Department of Bioengineering, University of Pennsylvania（宾夕法尼亚大学生物工程系）；Department of Computer and Information Science, University of Pennsylvania（宾夕法尼亚大学计算机与信息科学系）；Centre for Computational Biology, Duke-NUS Medical School（杜克-新加坡国立大学医学学校计算生物学中心）
Auxiliary Discrminator Sequence Generative Adversarial Networks (ADSeqGAN) for Few Sample Molecule Generation
School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States；School of Software \& Microelectronics, Peking University, Beijing, 100871, China
GraphVF: Controllable Protein-Specific 3D Molecule Generation with Variational Flow
Peking University（北京大学）；National Research Council Canada（加拿大国家研究委员会）；University of Ottawa（渥太华大学）；Mila - Québec AI Institute（Mila - 魁北克人工智能研究所）；HEC Montréal（蒙特利尔高等商学院）
Hotspot-Driven Peptide Design via Multi-Fragment Autoregressive Extension
Tsinghua University（清华大学）；University of Washington（华盛顿大学）；Massachusetts Institute of Technology（麻省理工学院）；University of Illinois Urbana-Champaign（伊利诺伊大学厄巴纳-香槟分校）；ByteDance Inc.（字节跳动公司）；Helixon Inc.（Helixon公司）
Reinforcement Learning Guides Generative Protein Language Models
Centre for Genomic Regulation, the Barcelona Institute of Science and Technology（基因组调控中心，巴塞罗那科学技术研究所）；Universitat Pompeu Fabra（庞培法布拉大学）；Universitat de Barcelona, Facultat de Farmàcia i Ciències de l’Alimentació（巴塞罗那大学，药学与食品科学学院）；Stanford University（斯坦福大学）；Arc Institute（ARC研究所）；Institució Catalana de Recerca i Estudis Avançats (ICREA)（加泰罗尼亚高级研究学院）
End-to-End Reverse Screening Identifies Protein Targets of Small Molecules Using HelixFold3
PaddleHelix Team（PaddleHelix团队）；Baidu Inc.（百度公司）；School of Software Engineering（软件工程学院）；Huazhong University of Science and Technology（华中科技大学）；School of Pharmacy, Tongji Medical College（药学院）
SIU: A Million-Scale Structural Small Molecule-Protein Interaction Dataset for Unbiased Bioactivity Prediction
Peking University（北京大学）；Institute for AI Industry Research (AIR), Tsinghua University（清华大学人工智能产业研究院）；School of Life Sciences, Tsinghua University（清华大学生命科学学院）；Department of Computer Science and Technology, Tsinghua University（清华大学计算机科学与技术系）
SurfDesign: Effective Protein Design on Molecular Surfaces
Stanford University（斯坦福大学）；Wuhan University of Science and Technology（武汉科技大学）；Yale University（耶鲁大学）；School of Medicine, Yale University（耶鲁大学医学院）；Hunan University（湖南大学）；Yuelushan Laboratory（岳麓实验室）；Kumo.AI；Toyota Technological Institute at Chicago（芝加哥技术研究所）
Scaling Structure Aware Virtual Screening to Billions of Molecules with SPRINT
University of Pittsburgh（匹兹堡大学）；Carnegie Mellon University（卡内基梅隆大学）；Mohamed Bin Zayed University of Artificial Intelligence（穆罕默德·本·扎耶德人工智能大学）；Petuum Inc.（Petuum公司）
MP2D: Constrained Monte Carlo Tree-Guided Diffusion for Multi-Objective Protein Sequence Design
College of Computer Science and Technology, Zhejiang University（浙江大学计算机科学与技术学院）；School of Mathematical Sciences, Zhejiang University（浙江大学数学科学学院）；State Key Laboratory of Transvascular Implantation Devices and TIDRI（血管植入器械国家重点实验室和TIDRI）；Zhejiang Key Laboratory of Medical Imaging Artificial Intelligence（浙江省医学影像人工智能重点实验室）
A 3D pocket-aware and evolutionary conserved interaction guided diffusion model for molecular optimization
School of Computer Science and Engineering, Sun Yat-sen University（中山大学计算机科学与工程学院）；School of Pharmaceutical Science, Sun Yat-sen University（中山大学药学院）；West China School of Pharmacy, Sichuan University（四川大学华西药学院）
Molecular dynamics without molecules: searching the conformational space of proteins with generative neural networks
Wayne State University（韦恩州立大学）；Univ. of Bari Aldo Moro（巴里大学阿尔多·莫罗分校）；National Research Council (CONICET)（国家研究委员会（CONICET））；Daruma Institute for Applied Intelligence（达摩应用智能研究所）
