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Despite the exciting progress in target-specific de novo protein binder design, peptide binder design remains challenging due to the flexibility of peptide structures and the scarcity of protein-peptide complex structure data. In this…

Biomolecules · Quantitative Biology 2024-09-04 Fanhao Wang , Yuzhe Wang , Laiyi Feng , Changsheng Zhang , Luhua Lai

Designing protein-binding proteins with high affinity is critical in biomedical research and biotechnology. Despite recent advancements targeting specific proteins, the ability to create high-affinity binders for arbitrary protein targets…

Machine Learning · Computer Science 2025-11-03 Zhenqiao Song , Tiaoxiao Li , Lei Li , Martin Renqiang Min

Target proteins that lack accessible binding pockets and conformational stability have posed increasing challenges for drug development. Induced proximity strategies, such as PROTACs and molecular glues, have thus gained attention as…

Peptide-based drugs can bind to protein interaction sites that small molecules often cannot, and are easier to produce than large protein drugs. However, designing effective peptide binders is difficult. A typical peptide has an enormous…

Biomolecules · Quantitative Biology 2025-11-19 Xiaoqiong Xia , Cesar de la Fuente-Nunez

Peptide design plays a pivotal role in therapeutics, allowing brand new possibility to leverage target binding sites that are previously undruggable. Most existing methods are either inefficient or only concerned with the target-agnostic…

Biomolecules · Quantitative Biology 2024-10-31 Xiangzhe Kong , Yinjun Jia , Wenbing Huang , Yang Liu

Generating peptides with desired properties is crucial for drug discovery and biotechnology. Traditional sequence-based and structure-based methods often require extensive datasets, which limits their effectiveness. In this study, we…

Quantitative Methods · Quantitative Biology 2024-08-19 Po-Yu Liang , Xueting Huang , Tibo Duran , Andrew J. Wiemer , Jun Bai

Diffusion and flow matching models have recently emerged as promising approaches for peptide binder design. Despite their progress, these models still face two major challenges. First, categorical sampling of discrete residue types…

Machine Learning · Computer Science 2025-11-20 Hao Qian , Shikui Tu , Lei Xu

Peptides, short chains of amino acids, interact with target proteins, making them a unique class of protein-based therapeutics for treating human diseases. Recently, deep generative models have shown great promise in peptide generation.…

Biomolecules · Quantitative Biology 2025-05-21 Jiahan Li , Tong Chen , Shitong Luo , Chaoran Cheng , Jiaqi Guan , Ruihan Guo , Sheng Wang , Ge Liu , Jian Peng , Jianzhu Ma

Peptides, short chains of amino acid residues, play a vital role in numerous biological processes by interacting with other target molecules, offering substantial potential in drug discovery. In this work, we present PepFlow, the first…

Biomolecules · Quantitative Biology 2024-06-04 Jiahan Li , Chaoran Cheng , Zuofan Wu , Ruihan Guo , Shitong Luo , Zhizhou Ren , Jian Peng , Jianzhu Ma

Peptides play a crucial role in the drug design and discovery whether as a therapeutic modality or a delivery agent. Non-natural amino acids (NNAAs) have been used to enhance the peptide properties from binding affinity, plasma stability to…

Structure-based drug design has seen significant advancements with the integration of artificial intelligence (AI), particularly in the generation of hit and lead compounds. However, most AI-driven approaches neglect the importance of…

Machine Learning · Computer Science 2025-11-10 Xinheng He , Yijia Zhang , Haowei Lin , Xingang Peng , Xiangzhe Kong , Mingyu Li , Jianzhu Ma

We present SeedProteo, a diffusion-based model for de novo all-atom protein design. We demonstrate how to repurpose a cutting-edge folding architecture into a powerful generative design framework by effectively integrating self-conditioning…

Biomolecules · Quantitative Biology 2026-02-25 Wei Qu , Yiming Ma , Fei Ye , Chan Lu , Yi Zhou , Kexin Zhang , Lan Wang , Minrui Gui , Quanquan Gu

Structure-based drug design (SBDD) aims to design small-molecule ligands that bind with high affinity and specificity to pre-determined protein targets. Generative SBDD methods leverage structural data of drugs in complex with their protein…

Biologists frequently desire protein inhibitors for a variety of reasons, including use as research tools for understanding biological processes and application to societal problems in agriculture, healthcare, etc. Immunotherapy, for…

Machine Learning · Computer Science 2024-11-04 Po-Yu Liang , Jun Bai

Designing protein sequences with specific biological functions and structural stability is crucial in biology and chemistry. Generative models already demonstrated their capabilities for reliable protein design. However, previous models are…

Machine Learning · Computer Science 2024-02-28 Lin Zongying , Li Hao , Lv Liuzhenghao , Lin Bin , Zhang Junwu , Chen Calvin Yu-Chian , Yuan Li , Tian Yonghong

Structure-based drug design (SBDD) aims to generate 3D ligand molecules that bind to specific protein targets. Existing 3D deep generative models including diffusion models have shown great promise for SBDD. However, it is complex to…

Biomolecules · Quantitative Biology 2024-03-01 Zhilin Huang , Ling Yang , Zaixi Zhang , Xiangxin Zhou , Yu Bao , Xiawu Zheng , Yuwei Yang , Yu Wang , Wenming Yang

Structure-based drug design (SBDD) aims to generate ligands that bind strongly and specifically to target protein pockets. Recent diffusion models have advanced SBDD by capturing the distributions of atomic positions and types, yet they…

Machine Learning · Computer Science 2026-02-11 Yue Jian , Curtis Wu , Danny Reidenbach , Aditi S. Krishnapriyan

The computational prediction and design of peptide binders targeting specific linear epitopes is crucial in biological and biomedical research, yet it remains challenging due to their highly dynamic nature and the scarcity of experimentally…

Biomolecules · Quantitative Biology 2024-10-23 Haowen Zhao , Francesco A. Aprile , Barbara Bravi

Recent advances in structure-based protein design have accelerated de novo binder generation, yet interfaces on large domains or spanning multiple domains remain challenging due to high computational cost and declining success with…

Biomolecules · Quantitative Biology 2025-10-03 Zhenfeng Deng , Ruijie Hou , Ningrui Xie , Mike Tyers , Michał Koziarski

In recent years, natural language processing (NLP) models have demonstrated remarkable capabilities in various domains beyond traditional text generation. In this work, we introduce PeptideGPT, a protein language model tailored to generate…

Machine Learning · Computer Science 2024-10-28 Aayush Shah , Chakradhar Guntuboina , Amir Barati Farimani
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