Protein Design

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Overview

Protein design aims to create or modify proteins—such as enzymes, binders, antibodies, and peptides—to perform useful functions while remaining stable and foldable. Methods include protein language models and inverse folding, diffusion and flow models that generate sequences or structures, and joint sequence–structure design conditioned on motifs, ligands, antigens, or text. Reinforcement learning, preference alignment, Bayesian optimization, and agent-based search can refine candidates using predicted properties or experimental feedback. Models now perform well on structural and in-silico benchmarks, but predicting real function remains difficult, making experimental validation, fair evaluation, diversity, and biosecurity important open challenges.

Latest papers

CardsList

103 papers12 papers in the last four weeks, down 33% on the four weeks before. 0.1% of all new papers.

  1. Does reflective LLM feedback survive a wet-lab-scale label budget?

    Nov 1, 2026Haoxuan Zeng, Xin LuoLLM Self-RefinementActive Learning

    University of Michigan, Ann Arbor, Michigan, USA

  2. Uncertainty Aware Quality-Diversity Optimization For Offline Biological Sequence Design

    Oct 31, 2026Alona Rimon, Hannah Janmohamed, Maxime Allard +1Quality-Diversity OptimizationUncertainty-Aware Exploration

    Imperial College London · Helical

  3. Computational De Novo Design of Miniprotein Candidate Neutralizers Targeting the IL-23 Cytokine Subunit p19

    Oct 23, 2026Raghav Paladugu, Fardina Fathmiul AlamProtein Binder DesignProtein Design

    Department of Computer Science, University of Maryland, College Park, MD, USA

  4. Trion-1: Unifying Language, Protein Sequence, and Structure with Diffusion Language Models

    Oct 22, 2026Tianyu Lu, Kaicheng Yang, Jiangtao Feng +7Protein Language ModelsProtein Structure Generation

  5. Multi-Objective Protein Optimization via Modular Diffusion Steering

    Oct 20, 2026Meir Roketlishvili, Felix Huber, Wenda Chu +2Multi-Objective OptimizationProtein Design

    Mohamed bin Zayed University of Artificial Intelligence, Abu Dhabi, UAE · California Institute of Technology, California, USA

  6. Poisoning the corpora of protein design systems during pre-training and retrieval

    Oct 15, 2026Charalampos Koilakos, Kimon-Antonios Provatas, Michail Patsakis +3Data Poisoning AttacksRAG Poisoning Attacks

    Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, Austin, TX, USA. · Department of Computer Science, The University of Texas at Austin · Institute for Fundamental Biomedical Research, BSRC “Alexander Fleming,”16672 Vari, Greece +1

  7. InstructPro2: Natural Language and Biological Grounding Guided De Novo Protein Design

    Oct 14, 2026Charles Novak, Zhenqiao Song, Chuan Li +2Protein DesignProtein Language Models

    Ray and Stephanie Lane Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA · Language Technologies Institute, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA · Lambda Inc, San Francisco, CA 94105, USA

  8. DC-Flow: Target-Conditioned Cyclic Peptide Design via Delayed-Coupling Flow Matching

    Oct 11, 2026Yitian Wang, Minjie Cheng, Yaning Cui +3Protein Structure GenerationMolecular Generation

    Gaoling School of Artificial Intelligence, Renmin University of China · DP Technology · Cyclon Therapeutics +2

  9. Designing Protein Structures from Natural Language

    Oct 9, 2026Joseph Lee, Yanjing Li, Bo Qiang +7Protein Structure GenerationProtein Design

    University of Washington · National University of Singapore · Allen Institute for AI (Ai2) +1

  10. DRYLAB-Bench: Benchmarking the Biosecurity Risk of Agentic LLM Mutation Design

    Oct 9, 2026Yuzhen Wang, Chunxiao Li, Baichen Le +6LLM SecurityAI Agent Safety Benchmarks

    Shanghai Artificial Intelligence Laboratory · Fudan University

  11. MARCO: The Radioactive Watermark for Protein Generative Models

    Oct 6, 2026Huajie Chen, Xin Guo, Yuchen Shi +7Robust WatermarkingDiffusion Model Watermarking

    Faculty of Data Science, City University of Macau. · CSIRO and Responsible AI Research (RAIR) Centre, Adelaide University.

  12. Bridging the Evidence-to-Execution Gap:A Reflective Agent for Multi-Objective Peptide Design

    Oct 5, 2026Haosen Zhang, Yang YangAI Agents for Scientific DiscoveryLarge Language Model-Guided Optimization

    School of Agriculture and Biology, Shanghai Jiao Tong University · School of Computer Science, Shanghai Jiao Tong University

  13. Predictor-Guided Latent Space Codon Optimization for Maximizing Protein Expression

    Oct 2, 2026Alberto Caron, Tianyu Cui, Dmytro S. Lituiev +13Protein DesignLatent Space Optimization

    Johnson & Johnson Innovative Medicine · Ellison Institute of Technology Oxford · New Theory AI

  14. Evaluator-in-the-Loop Monte Carlo Tree Search via LLM Agents for Motif Scaffolding in Protein Design

    Oct 2, 2026Haotian Hu, Oguzhan Gungordo, Siheng Xiong +1Protein DesignMonte Carlo Tree Search

    Georgia Institute of Technology

  15. Generative modeling of intrinsically disordered protein regions by reinforcing sparse autoencoder features

    Oct 1, 2026Jason X. Liu, Sebastian Ibarraran, Frank Hu +7Autoregressive Language ModelingSparse Autoencoders

    Stanford University

  16. CODesign: Consistency from Data to Trajectory in All-Atom Protein Binder Co-Design

    Oct 1, 2026Yuanle Mo, Bo Qiang, Haitao Lin +4Molecular GenerationProtein Design

    Valhalla Technology · The Chinese University of Hong Kong · University of Washington +2

  17. pCoMole: Pareto-Constrained Molecule Editing with Discrete Flows

    Oct 1, 2026Tong Chen, Maximilian Holsman, Lin Zhao +1Constrained Generative ModelingProtein Design

    Department of Computer and Information Science, University of Pennsylvania · Department of Computer Science, Duke University · Department of Bioengineering, University of Pennsylvania

  18. Structure-aware Reinforcement Learning for Protein Directed Evolution

    Sep 30, 2026Zikun Nie, Suyuan Zhao, Yizhen Luo +2Protein Design

    Institute of AI Industry Research (AIR), Tsinghua University · Department of Computer Science and Technology, Tsinghua University · Pharmolix Inc.

  19. Feedback-Calibrated Protein Optimization with Batch-Aligned Tail Arbitration

    Sep 29, 2026Zefeng Lin, Xianyong Fang, Tianfan Fu +1Molecular OptimizationProtein Design

    School of Computer Science and Technology, University of Science and Technology of China, Hefei, Anhui, China

  20. From Surfaces to Volumes: Registered Geometry for Protein Representation Learning

    Sep 28, 2026Siyuan Chen, Cai Zhou, Jinrui Zhang +8Protein-Protein Interaction Prediction3D Representation Learning

    University of British Columbia · Massachusetts Institute of Technology · Carnegie Mellon University +2

  21. Mirror-Score: Calibrated, Inference-only Scoring Exposes the Limits of Sequence-compatibility Ranking in D-peptide Design

    Sep 28, 2026Jiada LiProtein-Ligand Binding Affinity PredictionProtein Design

    AI Scientist, Albany, NY, USA, 12205

  22. AbGaze: Attentive Geometric Representation Learning for End-to-End Antibody Design

    Sep 28, 2026Jiashuo Wang, Siqi Fan, Yizhen Luo +1Geometric Representation LearningMolecular Generation

    Institute for AI Industry Research (AIR), Tsinghua University · Department of Computer Science and Technology, Tsinghua University · PharMolix Inc.

  23. Continuous Variational Synthesis

    Sep 28, 2026Alan N. Amin, Mattia G. Gollub, Andrei Slabodkin +2Variational AutoencodersConstrained Generative Modeling

    JURA Bio, Inc. Boston, MA 02125, USA

  24. SPINET: Sheaf Protein Inverse Folding Network

    Sep 28, 2026Jens Lundsgaard, Colin Mikulski, Zhixuan Yan +1Protein Design

    Department of Computer Sciences, University of Wisconsin–Madison, Madison, WI, USA · Department of Mathematics, University of Wisconsin–Madison, Madison, WI, USA · Department of Biomedical Engineering, University of Wisconsin–Madison, Madison, WI, USA +4

  25. Robust Biomolecular Complex Design Across Protein Conformational Landscapes

    Sep 27, 2026Qingyuan Zeng, Zongqi Xu, Anglin Liu +7Test-Time AdaptationMulti-Objective Evolutionary Optimization

    The Hong Kong University of Science and Technology (Guangzhou) · Southwest Minzu University · Guangzhou University of Chinese Medicine

  26. PhiFold: Towards Dynamic Protein Design with Physics-Structured Covariance Modeling

    Sep 26, 2026Yutian Liu, Mujie Lin, LanqianZhang +4Protein DesignProtein Structure Generation

    School of Computer Science, Peking University, Beijing, China · School of Electronic and Computer Engineering, Peking University, Shenzhen, China · School of Life Sciences, Tsinghua University, Beijing 100084, China +2

  27. Spectral Feedback for Test-Time Alignment of Protein Diffusion Models

    Sep 24, 2026Shai Dickman, Mert Cemri, Landon Butler +1Diffusion Model AlignmentProtein Design

    Department of Electrical Engineering and Computer Sciences University of California, Berkeley

  28. PFArena: Benchmarking Language Models for Protein Modification

    Sep 24, 2026Yawen Ouyang, Xinbo Zhang, Ziyuan Ma +15Protein Fitness PredictionProtein Language Models

    Shanghai Artificial Intelligence Laboratory · Generative Symbolic Intelligence Lab (GenSI), Tsinghua University · Institute for AI Industry Research (AIR), Tsinghua University +1

  29. TorchCraft: Unified binder design by inverting an all-atom structure predictor

    Sep 17, 2026TorchCraft Team, Yu Liu, Zhouhanyu Shen +8Molecular GenerationProtein Design

    Changping Laboratory, Beijing, China

  30. When Edit Flows are Edit Jumps: replicating Edit Flows and EvoFlows

    Sep 16, 2026Gabriel Bénédict, Melanie Buechler, Gerard Riera-Solà +3Generative ModelingProtein Design

    Visium, Switzerland