Structure-Based Drug Design

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6 papers in the last four weeks, up 100% on the four weeks before. 0.1% of all new papers.

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CausalBind: Causal Modeling and Learning for Protein-Molecule Virtual Screening
Oct 5, 2026Loka Li, Jin Tian, Kun ZhangCausal Representation Learning Structured Sparsity
Mohamed bin Zayed University of Artificial Intelligence · Carnegie Mellon University
Auditable Algebraic Counting Field for Cryptic-Pocket Detection from Apo Structures
Oct 1, 2026Shan Yu, Xuening WuInterpretable ML Structure-Based Drug Design
Pfizer, Shanghai, China
RIDE: Reference-Anchored Inference-Time Diffusion Editing for Scaffold Hopping
Sep 28, 2026Ruoxi Gao, Frazier N. Baker, Trieu Nguyen +1Diffusion Guidance Structure-Based Drug Design
Department of Computer Science and Engineering, The Ohio State University · Department of Biomedical Informatics, The Ohio State University · Translational Data Analytics Institute, The Ohio State University +1
One Sequence, Many Decodings: CAGenMol-2 Recasts Drug Design as Masked Molecular Inference
Sep 28, 2026Yanting Li, Enyan Dai, Lei Wang +2Molecular Optimization Masked Diffusion Models
The Hong Kong University of Science and Technology (Guangzhou) · Jinan University, Guangzhou
Ensemble-Conditioned Molecular Design
Sep 14, 2026Ross Irwin, Alessandro Tibo, Jon Paul Janet +1Molecular Optimization Structure-Based Drug Design
Molecular AI Discovery Sciences, R&D AstraZeneca Gothenburg, Sweden · Department of Computer Science and Engineering Chalmers University of Technology and University of Gothenburg Gothenburg, Sweden
A Systematic Evaluation of Molecule Generation Models for De Novo Drug Design: From Benchmarks to Practical Insights
Sep 9, 2026Xinrui Xu, Xueer Wang, Dan Luo +2Structure-Based Drug Design Molecular Generation
School of Computer Science, Xiangtan University, Xiangtan 411105, China · College of Computer Science and Electronic Engineering, Hunan University, Changsha 410082, China · School of Chinese Medicine, Hong Kong Baptist University, 15 Baptist University Road, Kowloon Tong 999077, Kowloon, Hong Kong SAR, China
PocketVE: Stable and Property-Guided Structure-Based Drug Design with Variance-Exploding Diffusion
Sep 8, 2026Peining Zhang, Jinbo BiDiffusion Model Guidance Structure-Based Drug Design
University of Connecticut Storrs, Connecticut 06269, USA
Language-Informed Flow Matching for Trend-Guided Structure-Based 3D Molecular Generation
Aug 31, 2026Tianyu Gao, Zhikai Su, Jiashu Li +5Flow Matching Structure-Based Drug Design
1City University of Hong Kong · 2The University of Hong Kong · 3Stanford University
A Modular Agentic Framework for Synthetically Constrained Multi-Objective Hit-to-Lead Optimization
Aug 11, 2026Kelvin P. Idanwekhai, Enes Kelestemur, Benjamin Strickland +6Molecular Optimization LLM Agent Orchestration
Department of Chemistry, UNC Chapel Hill, Chapel Hill, NC, USA · Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy at UNC, Chapel Hill, NC, USA · Department of Applied Physical Sciences, UNC Chapel Hill, NC, USA +1
RAVEN: Frozen Random Graph Reservoirs with Physics-Informed Interaction Fingerprints for Protein-Ligand Binding Affinity Prediction
Aug 10, 2026Qingyang Zou, Jiaye Huang, Hangbo Xie +3Protein-Ligand Binding Affinity Prediction Graph Neural Networks
School of Science, China Pharmaceutical University, Nanjing, 210009, China · School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210009, China
Scalable High-Fidelity Macromolecular Docking for GPU-Accelerated Supercomputers
Aug 7, 2026Xiangyu Meng, Peng Chen, Mingzhen Li +7GPU Kernel Optimization GPU Acceleration
College of Computer Science and Technology, Shandong Key Laboratory of Intelligent Oil & Gas Industrial Software, China University of Petroleum (East China), Qingdao, China · A*STAR Institute of Advanced Intelligence and Computing, Singapore · RIKEN Center for Computational Science, Kobe, Japan +2
Fused Bayesian Flow Networks for Dual-Target Molecular Design
Aug 2, 2026Jingyuan Zhou, Shikui Tu, Lei XuStructure-Based Drug Design Molecular Generation
School of Computer Science, Shanghai Jiao Tong University · Guangdong Laboratory of Artificial Intelligence and Digital Economy (SZ)
DBMol: Design of High-Affinity, Target-Specific Small Molecules through Structure Prediction Models
Jul 21, 2026Yiming Qin, Kai Yi, Miruna Cretu +3Protein-Ligand Binding Affinity Prediction Molecular Optimization
EPFL, Switzerland · MRC-LMB, UK · University of Cambridge, UK
Do Language Models Dream of Binding Molecules? Benchmarking LLMs under Spatial Constraints
Jul 20, 2026Thomas MacDougall, Maksim Kuznetsov, Roman Schutski +5Constrained Generative Modeling LLM Evaluation
Insilico Medicine Canada Inc. · Insilico Medicine Hong Kong Ltd. · Insilico Medicine AI Limited
Generating Developable 3D Molecules via Pocket-Conditioned Diffusion and Property-Aware Optimization
Jul 14, 2026Ruoxi Gao, Jiangweizhi Peng, Ziqi Chen +10Molecular Optimization Structure-Based Drug Design
Computer Science and Engineering, The Ohio State University, Columbus, OH 43210. · Industrial and System Engineering, University of Minnesota, Minneapolis, MN 55455. · Google Cloud, Google LLC, Mountain View, CA 94043. +6
Q-Score: A Quantum-Native Scoring Function for Molecular Docking
Jul 2, 2026Kangyu Zheng, Yidong Zhou, Ruihao Li +3Protein-Ligand Binding Affinity Prediction Structure-Based Drug Design
Department of Computer Science and Engineering The Chinese University of Hong Kong Shatin, N.T., Hong Kong SAR · Department of Electrical and Computer Engineering Rutgers University Piscataway, NJ · Computational Life Sciences Cleveland Clinic Cleveland, OH +1
Sesame: Structure-Aware Molecular Generation via Spatial Density-Map Conditioning
Jun 22, 2026Konstantin Yatsenko, Arvind ThiagarajanMolecular Optimization Structure-Based Drug Design
Tessel Biosciences, Inc., 750 Main Street, Cambridge, MA 02139
Multigrid Training for Molecular Generation using Graph Neural Networks
Jun 21, 2026Zixuan Ling, Paula Mercurio, Di LiuStructure-Based Drug Design 3D Molecular Generation
Department of Mathematics, Michigan State University, East Lansing, MI. · Department of Mathematics, Hamline University, Saint Paul, MN.
ShallowBench: Benchmarking Generative Drug Design Models on Shallow-Pocket Targets
Jun 4, 2026Saket Reddy, Shiwei LiuBenchmark Design Structure-Based Drug Design
University of Illinois - Urbana-Champaign
SpliceBind: Isoform-Aware Prediction of Binding Pocket Druggability
Jun 1, 2026Bryan Cheng, Austin Jin, Joshua ChangStructure-Based Drug Design Drug Discovery
Independent Researcher USA
Fine-Tuning Diffusion Models for Molecular Generation via Reinforcement Learning and Fast Sampling
May 31, 2026Guang Lin, Shikui Tu, Lei XuMolecular Optimization Diffusion Model Fine-Tuning
Department of Computer Science and Engineering, Shanghai Jiao Tong University, Shanghai, China · Guangdong Laboratory of Artificial Intelligence and Digital Economy (SZ), Shenzhen, Guangdong, China
Probe Before You Edit: Probing-Guided Molecular Optimization for LLM Agents in Structure-Based Drug Design
May 30, 2026Zaifei Yang, Weiyu Chen, Yaqing Wang +1Molecular Optimization Multi-Agent LLM Systems
1The Hong Kong University of Science and Technology · 2City University of Hong Kong · Beijing Institute of Mathematical Sciences and Applications
MolLingo: Molecule-Native Representations for LLM-Powered Scientific Agents
May 27, 2026Thao Nguyen, Heng JiMolecular Optimization Multi-Agent LLM Systems
Siebel School of Computing and Data Science, University of Illinois Urbana-Champaign
An accurate nucleic acid-small molecule docking framework via geometric deep learning with large-scale pretraining
May 22, 2026Shi Li, Xujun Zhang, Mingquan Liu +5Structure-Based Drug Design Drug Discovery
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, P. R. China · College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, P. R. China · Faculty of Health Sciences, University of Macau, Macau SAR, China +4
Fine-tuning Pocket-Aware Diffusion Models via Denoising Policy Optimization
May 17, 2026Yuan Xue, Daniel Kudenko, Megha KhoslaMolecular Optimization Diffusion Model Fine-Tuning
L3S Research Center, Hanover, Germany · Delft University of Technology, Delft, Netherlands
From Holo Pockets to Electron Density: GPT-style Drug Design with Density
May 9, 2026Jiahao Chen, Letian Gao, Yanhao Zhu +4Structure-Based Drug Design 3D Molecular Generation
Gaoling School of Artificial Intelligence, Renmin University of China, Beijing, China · Beijing Key Laboratory of Research on Large Models and Intelligent Governance, Beijing, China · Engineering Research Center of Next Generation Intelligent Search and Recommendation, MOE, Beijing, China +3
Computational Design and Experimental Validation of Photoactive PARP1 Inhibitors
Apr 27, 2026Simon Axelrod, Miroslav Kašpar, Kristýna Jelínková +8Molecular Optimization Structure-Based Drug Design
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, 02138 · Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139 · Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo nám. 2, 160 00 Prague 6, Czech Republic
Structure-guided molecular design with contrastive 3D protein-ligand learning
Apr 21, 2026Carles Navarro, Philipp Tholke, Gianni de FabritiisContrastive Learning Virtual Screening
Acellera Labs, C/ Doctor Trueta 183, 08005 Barcelona, Spain · Computational Science Laboratory, Universitat Pompeu Fabra, PRBB, C/ Doctor Aiguader 88, 08003 Barcelona, Spain · Instituci´o Catalana de Recerca i Estudis Avan¸cats (ICREA), Passeig Llu´ıs Companys 23, 08010 Barcelona, Spain
KinetiDiff: Docking-Guided Diffusion for De Novo ACVR1 Inhibitor Design in Fibrodysplasia Ossificans Progressiva
Apr 17, 2026Aaryan PatelMolecular Optimization Diffusion Guidance
Saugus High School, Santa Clarita, CA

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CausalBind: Causal Modeling and Learning for Protein-Molecule Virtual Screening

Loka Li, Jin Tian, Kun Zhang

Mohamed bin Zayed University of Artificial Intelligence · Carnegie Mellon University

Causal Representation Learning Structured Sparsity Structure-Based Drug Design Causal Identifiability Molecular Representation Learning

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Protein-molecule virtual screening is increasingly cast as a problem of representation learning in a shared embedding space. Existing methods rely on dense holistic alignment, entangling invariant binding determinants with nuisance correlations and limiting transfer to new targets. It has been noted that binding in protein-molecule systems involves sparse cross-modality interactions: binding is governed by a small contact interface and a few decisive local interactions (e.g., hydrogen bonds, hydrophobic contacts, and salt bridges) rather than the global structures of the protein and molecule. We hypothesize that uncovering and leveraging sparse interaction patterns is critical for generalization beyond the training data, as these patterns are reusable and expected to improve performance across different scenarios. In this paper, we aim to identify and leverage sparse interaction patterns, and verify our hypothesis. Since the training data contain only observed binding pairs, we formalize this prior via a V-structure causal model under Heckman-style selection, and establish three theoretical results: (i) the latent concepts of interacting proteins and molecules are not identifiable without appropriate sparsity constraints; (ii) these concepts and their sparse interactions are component-wise identifiable under structural sparsity conditions; and (iii) a low-rank relaxation of these conditions yields subspace identifiability of the concepts and interactions. Inspired by these principles, we propose CausalBind with three implementation variants. Extensive experiments on DUD-E and LIT-PCBA benchmarks show that all variants consistently outperform strong retrieval baselines, with the largest gains on LIT-PCBA early enrichment, and further generalize to target- and scaffold-level out-of-distribution splits. Code is available at https://github.com/lokali/CausalBind.

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