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Related papers: FlexSBDD: Structure-Based Drug Design with Flexibl…

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Dual-target therapeutic strategies have become a compelling approach and attracted significant attention due to various benefits, such as their potential in overcoming drug resistance in cancer therapy. Considering the tremendous success…

Machine Learning · Computer Science 2024-11-27 Xiangxin Zhou , Jiaqi Guan , Yijia Zhang , Xingang Peng , Liang Wang , Jianzhu Ma

Molecular docking, a key technique in structure-based drug design, plays pivotal roles in protein-ligand interaction modeling, hit identification and optimization, in which accurate prediction of protein-ligand binding mode is essential.…

Biomolecules · Quantitative Biology 2023-12-20 Jintao Zhu , Zhonghui Gu , Jianfeng Pei , Luhua Lai

Proteins adopt multiple structural conformations to perform their diverse biological functions, and understanding these conformations is crucial for advancing drug discovery. Traditional physics-based simulation methods often struggle with…

Biomolecules · Quantitative Biology 2025-03-14 Jiarui Lu , Xiaoyin Chen , Stephen Zhewen Lu , Chence Shi , Hongyu Guo , Yoshua Bengio , Jian Tang

Developing bioactive molecules remains a central, time- and cost-heavy challenge in drug discovery, particularly for novel targets lacking structural or functional data. Pharmacophore modeling presents an alternative for capturing the key…

Machine Learning · Computer Science 2025-05-16 Amira Alakhdar , Barnabas Poczos , Newell Washburn

The goal of structure-based drug discovery is to find small molecules that bind to a given target protein. Deep learning has been used to generate drug-like molecules with certain cheminformatic properties, but has not yet been applied to…

Quantitative Methods · Quantitative Biology 2022-01-27 Matthew Ragoza , Tomohide Masuda , David Ryan Koes

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

Designing 3D ligands within a target binding site is a fundamental task in drug discovery. Existing structured-based drug design methods treat all ligand atoms equally, which ignores different roles of atoms in the ligand for drug design…

Biomolecules · Quantitative Biology 2024-03-14 Jiaqi Guan , Xiangxin Zhou , Yuwei Yang , Yu Bao , Jian Peng , Jianzhu Ma , Qiang Liu , Liang Wang , Quanquan Gu

To design a drug given a biological molecule by using deep learning methods, there are many successful models published recently. People commonly used generative models to design new molecules given certain protein. LiGAN was regarded as…

Machine Learning · Computer Science 2022-11-15 Haotian Zhang , Linxiaoyi Wan

De novo molecular design has facilitated the exploration of large chemical space to accelerate drug discovery. Structure-based de novo method can overcome the data scarcity of active ligands by incorporating drug-target interaction into…

Biomolecules · Quantitative Biology 2022-09-16 Yaqin Li , Lingli Li , Yongjin Xu , Yi Yu

Structure-based drug design (SBDD) leverages the 3D structure of biomolecular targets to guide the creation of new therapeutic agents. Recent advances in generative models, including diffusion models and geometric deep learning, have…

Biomolecules · Quantitative Biology 2025-01-28 Ali Khodabandeh Yalabadi , Mehdi Yazdani-Jahromi , Ozlem Ozmen Garibay

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

Protein structure prediction is pivotal for understanding the structure-function relationship of proteins, advancing biological research, and facilitating pharmaceutical development and experimental design. While deep learning methods and…

Machine Learning · Computer Science 2024-12-30 Kaihui Cheng , Ce Liu , Qingkun Su , Jun Wang , Liwei Zhang , Yining Tang , Yao Yao , Siyu Zhu , Yuan Qi

Recent advances in Structure-based Drug Design (SBDD) have leveraged generative models for 3D molecular generation, predominantly evaluating model performance by binding affinity to target proteins. However, practical drug discovery…

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

We propose a hierarchical protein backbone generative model that separates coarse and fine-grained details. Our approach called LSD consists of two stages: sampling latents which are decoded into a contact map then sampling atomic…

Quantitative Methods · Quantitative Biology 2025-04-15 Jason Yim , Marouane Jaakik , Ge Liu , Jacob Gershon , Karsten Kreis , David Baker , Regina Barzilay , Tommi Jaakkola

The ultimate goal of drug design is to find novel compounds with desirable pharmacological properties. Designing molecules retaining particular scaffolds as the core structures of the molecules is one of the efficient ways to obtain…

Quantitative Methods · Quantitative Biology 2019-09-06 Yibo Li , Jianxing Hu , Yanxing Wang , Jielong Zhou , Liangren Zhang , Zhenming Liu

Virtual screening (VS) is an essential task in drug discovery, focusing on the identification of small-molecule ligands that bind to specific protein pockets. Existing deep learning methods, from early regression models to recent…

Machine Learning · Computer Science 2025-11-11 Bowei He , Bowen Gao , Yankai Chen , Yanyan Lan , Chen Ma , Philip S. Yu , Ya-Qin Zhang , Wei-Ying Ma

Engineering molecules to exhibit precise 3D intermolecular interactions with their environment forms the basis of chemical design. In ligand-based drug design, bioisosteric analogues of known bioactive hits are often identified by virtually…

Biomolecules · Quantitative Biology 2025-03-18 Keir Adams , Kento Abeywardane , Jenna Fromer , Connor W. Coley

Proteins in complex with small molecule ligands represent the core of structure-based drug discovery. However, three-dimensional representations are absent from most deep-learning-based generative models. We here present a graph-based…

Biomolecules · Quantitative Biology 2022-04-07 Seung-gu Kang , Jeffrey K. Weber , Joseph A. Morrone , Leili Zhang , Tien Huynh , Wendy D. Cornell

Drug discovery is a complex, resource-intensive process requiring significant time and cost to bring new medicines to patients. Many generative models aim to accelerate drug discovery, but few produce synthetically accessible molecules.…

Machine Learning · Computer Science 2025-01-30 Zygimantas Jocys , Zhanxing Zhu , Henriette M. G. Willems , Katayoun Farrahi