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Peptides offer great biomedical potential and serve as promising drug candidates. Currently, the majority of approved peptide drugs are directly derived from well-explored natural human peptides. It is quite necessary to utilize advanced…

Biomolecules · Quantitative Biology 2024-01-29 Yipin Lei , Xu Wang , Meng Fang , Han Li , Xiang Li , Jianyang Zeng

Structure-based drug design (SBDD), which aims to generate molecules that can bind tightly to the target protein, is an essential problem in drug discovery, and previous approaches have achieved initial success. However, most existing…

Machine Learning · Computer Science 2024-04-04 Xinze Li , Penglei Wang , Tianfan Fu , Wenhao Gao , Chengtao Li , Leilei Shi , Junhong Liu

Effective generation of molecular structures, or new chemical entities, that bind to target proteins is crucial for lead identification and optimization in drug discovery. Despite advancements in atom- and motif-wise deep learning models…

Machine Learning · Computer Science 2025-03-04 Guanlue Li , Chenran Jiang , Ziqi Gao , Yu Liu , Chenyang Liu , Jiean Chen , Yong Huang , Jia Li

Structure-based protein design has attracted increasing interest, with numerous methods being introduced in recent years. However, a universally accepted method for evaluation has not been established, since the wet-lab validation can be…

Quantitative Methods · Quantitative Biology 2023-12-04 Chuanrui Wang , Bozitao Zhong , Zuobai Zhang , Narendra Chaudhary , Sanchit Misra , Jian Tang

Protein inverse folding aims to identify viable amino acid sequences that can fold into given protein structures, enabling the design of novel proteins with desired functions for applications in drug discovery, enzyme engineering, and…

Quantitative Methods · Quantitative Biology 2024-11-05 Taoyu Wu , Yu Guang Wang , Yiqing Shen

Traditional drug discovery relies on rounds of screening millions of candidate molecules with low success rates, making drug discovery time and resource intensive. To overcome this screening bottleneck, we introduce Latent-X, an all-atom…

Peptide self-assembly prediction offers a powerful bottom-up strategy for designing biocompatible, low-toxicity materials for large-scale synthesis in a broad range of biomedical and energy applications. However, screening the vast sequence…

Biomolecules · Quantitative Biology 2026-04-23 Nuno Costa , Julija Zavadlav

Structure-based drug design (SBDD), which aims to generate 3D ligand molecules binding to target proteins, is a fundamental task in drug discovery. Existing SBDD methods typically treat protein as rigid and neglect protein structural change…

Biomolecules · Quantitative Biology 2024-10-01 Zaixi Zhang , Mengdi Wang , Qi Liu

Generative models of macromolecules carry abundant and impactful implications for industrial and biomedical efforts in protein engineering. However, existing methods are currently limited to modeling protein structures or sequences,…

Biomolecules · Quantitative Biology 2024-01-15 Alex Morehead , Jeffrey Ruffolo , Aadyot Bhatnagar , Ali Madani

Protein-protein interactions (PPIs) are governed by surface complementarity and hydrophobic interactions at protein interfaces. However, designing diverse and physically realistic protein structure and surfaces that precisely complement…

Machine Learning · Computer Science 2025-11-24 Guanlue Li , Xufeng Zhao , Fang Wu , Sören Laue

Dual-target structure-based drug design aims to generate a single ligand together with two pocket-specific binding poses, each compatible with a corresponding target pocket, enabling polypharmacological therapies with improved efficacy and…

Machine Learning · Computer Science 2026-03-09 Jianliang Wu , Anjie Qiao , Zhen Wang , Zhewei Wei , Sheng Chen

Designing novel protein sequences for a desired 3D topological fold is a fundamental yet non-trivial task in protein engineering. Challenges exist due to the complex sequence--fold relationship, as well as the difficulties to capture the…

Machine Learning · Computer Science 2021-06-25 Yue Cao , Payel Das , Vijil Chenthamarakshan , Pin-Yu Chen , Igor Melnyk , Yang Shen

Cyclic peptides, characterized by geometric constraints absent in linear peptides, offer enhanced biochemical properties, presenting new opportunities to address unmet medical needs. However, designing target-specific cyclic peptides…

Machine Learning · Computer Science 2025-07-15 Dapeng Jiang , Xiangzhe Kong , Jiaqi Han , Mingyu Li , Rui Jiao , Wenbing Huang , Stefano Ermon , Jianzhu Ma , Yang Liu

Many crucial biological processes rely on networks of protein-protein interactions. Predicting the effect of amino acid mutations on protein-protein binding is vital in protein engineering and therapeutic discovery. However, the scarcity of…

Biomolecules · Quantitative Biology 2023-11-01 Shiwei Liu , Tian Zhu , Milong Ren , Chungong Yu , Dongbo Bu , Haicang Zhang

Generating novel active molecules for a given protein is an extremely challenging task for generative models that requires an understanding of the complex physical interactions between the molecule and its environment. In this paper, we…

Generating molecules that bind to specific protein targets via diffusion models has shown good promise for structure-based drug design and molecule optimization. Especially, the diffusion models with binding interaction guidance enables…

Machine Learning · Computer Science 2025-05-12 Anjie Qiao , Hao Zhang , Qianmu Yuan , Qirui Deng , Jingtian Su , Weifeng Huang , Huihao Zhou , Guo-Bo Li , Zhen Wang , Jinping Lei

Diffusion models offer a powerful means of capturing the manifold of realistic protein structures, enabling rapid design for protein engineering tasks. However, existing approaches observe critical failure modes when precise constraints are…

Biomolecules · Quantitative Biology 2026-03-27 Jacob K. Christopher , Austin Seamann , Jingyi Cui , Sagar Khare , Ferdinando Fioretto

Modeling the interaction between proteins and ligands and accurately predicting their binding structures is a critical yet challenging task in drug discovery. Recent advancements in deep learning have shown promise in addressing this…

Machine Learning · Computer Science 2024-01-10 Qizhi Pei , Kaiyuan Gao , Lijun Wu , Jinhua Zhu , Yingce Xia , Shufang Xie , Tao Qin , Kun He , Tie-Yan Liu , Rui Yan

Generative models for de novo protein backbone design have achieved remarkable success in creating novel protein structures. However, these diffusion-based approaches remain computationally intensive and slower than desired for large-scale…

Machine Learning · Computer Science 2026-02-09 Shentong Mo , Lanqing Li

The design of \emph{de novo} functional proteins that bind specific ligand molecules is paramount in therapeutics and bio-engineering. A critical yet formidable task in this endeavor is the design of the protein pocket, which is the cavity…

Biomolecules · Quantitative Biology 2023-10-23 Zaixi Zhang , Zepu Lu , Zhongkai Hao , Marinka Zitnik , Qi Liu