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Proteolysis-targeting chimeras (PROTACs) represent a promising therapeutic modality that induces targeted protein degradation by hijacking the ubiquitin-proteasome system. However, rational PROTAC design remains challenging due to the…

Quantitative Methods · Quantitative Biology 2026-05-20 Stefano Ribes , Nils Dunlop , Rocío Mercado

PROteolysis TArgeting Chimeras (PROTACs) are an emerging therapeutic modality for degrading a protein of interest (POI) by marking it for degradation by the proteasome. Recent developments in artificial intelligence (AI) suggest that deep…

Quantitative Methods · Quantitative Biology 2022-11-08 Divya Nori , Connor W. Coley , Rocío Mercado

Proteolysis-Targeting Chimeras (PROTACs) represent a novel class of small molecules which are designed to act as a bridge between an E3 ligase and a disease-relevant protein, thereby promoting its subsequent degradation. PROTACs are…

Machine Learning · Computer Science 2023-06-16 Rebecca M. Neeser , Mehmet Akdel , Daniel Kovtun , Luca Naef

Proteolysis targeting chimera (PROTAC) is a novel drug modality that facilitates the degradation of a target protein by inducing proximity with an E3 ligase. In this work, we present a new computational framework to model the cooperativity…

Biological Physics · Physics 2023-01-10 Huanghao Mai , Matthew H. Zimmer , Thomas F. Miller

PROTACs are a promising therapeutic modality that harnesses the cell's built-in degradation machinery to degrade specific proteins. Despite their potential, developing new PROTACs is challenging and requires significant domain expertise,…

Quantitative Methods · Quantitative Biology 2024-09-30 Stefano Ribes , Eva Nittinger , Christian Tyrchan , Rocío Mercado

Targeted protein degradation (TPD) is a rapidly growing field in modern drug discovery that aims to regulate the intracellular levels of proteins by harnessing the cell's innate degradation pathways to selectively target and degrade…

Biomolecules · Quantitative Biology 2024-06-25 Yossra Gharbi , Rocío Mercado

The imperfect modeling of ternary complexes has limited the application of computer-aided drug discovery tools in PROTAC research and development. In this study, an AI-assisted approach for PROTAC molecule design pipeline named LM-PROTAC…

Quantitative Methods · Quantitative Biology 2024-12-16 Jinsong Shao , Qineng Gong , Zeyu Yin , Yu Chen , Yajie Hao , Lei Zhang , Linlin Jiang , Min Yao , Jinlong Li , Fubo Wang , Li Wang

The design of protein sequences with desired functionalities is a fundamental task in protein engineering. Deep generative methods, such as autoregressive models and diffusion models, have greatly accelerated the discovery of novel protein…

Machine Learning · Computer Science 2025-04-16 Zitai Kong , Yiheng Zhu , Yinlong Xu , Hanjing Zhou , Mingzhe Yin , Jialu Wu , Hongxia Xu , Chang-Yu Hsieh , Tingjun Hou , Jian Wu

Protein--ligand docking is widely used in structure-based discovery, but routine studies often fail at the workflow level rather than at the scoring level. Receptor cleaning, ligand preparation, file conversion, box definition, run…

Quantitative Methods · Quantitative Biology 2026-04-24 Tieu-Long Phan , Lai Hoang Son Le , Thanh-An Pham , Nhu-Ngoc Nguyen Song , Tuyet-Minh Phan , Tuyen Ngoc Truong

Predicting the binding structure of a small molecule ligand to a protein -- a task known as molecular docking -- is critical to drug design. Recent deep learning methods that treat docking as a regression problem have decreased runtime…

Biomolecules · Quantitative Biology 2023-02-14 Gabriele Corso , Hannes Stärk , Bowen Jing , Regina Barzilay , Tommi Jaakkola

Molecular docking is a key computational tool utilized to predict the binding conformations of small molecules to protein targets, which is fundamental in the design of novel drugs. Despite recent advancements in geometric deep…

Biomolecules · Quantitative Biology 2023-12-01 Jiaxian Yan , Zaixi Zhang , Kai Zhang , Qi Liu

Recently, extensive deep learning architectures and pretraining strategies have been explored to support downstream protein applications. Additionally, domain-specific models incorporating biological knowledge have been developed to enhance…

Biomolecules · Quantitative Biology 2026-03-03 Shuo Yan , Yuliang Yan , Bin Ma , Chenao Li , Haochun Tang , Jiahua Lu , Minhua Lin , Yuyuan Feng , Enyan Dai

Lightweight inference is critical for biomolecular structure prediction and downstream tasks, enabling efficient real-world deployment and inference-time scaling for large-scale applications. While AF3 and its variants (e.g., Protenix,…

Quantitative Methods · Quantitative Biology 2025-10-17 Bo Qiang , Chengyue Gong , Xinshi Chen , Yuxuan Zhang , Wenzhi Xiao

Understanding how proteins structurally interact is crucial to modern biology, with applications in drug discovery and protein design. Recent machine learning methods have formulated protein-small molecule docking as a generative problem…

Accelerating molecular docking -- the process of predicting how molecules bind to protein targets -- could boost small-molecule drug discovery and revolutionize medicine. Unfortunately, current molecular docking tools are too slow to screen…

Computational docking methods can provide structural models of protein-protein complexes, but protein backbone flexibility upon association often thwarts accurate predictions. In recent blind challenges, medium or high accuracy models were…

Biomolecules · Quantitative Biology 2020-12-29 Ameya Harmalkar , Jeffrey J. Gray

Understanding the dynamic nature of protein structures is essential for comprehending their biological functions. While significant progress has been made in predicting static folded structures, modeling protein motions on microsecond to…

Accurate prediction of protein-ligand binding structures, a task known as molecular docking is crucial for drug design but remains challenging. While deep learning has shown promise, existing methods often depend on holo-protein structures…

Biomolecules · Quantitative Biology 2024-02-22 Yufei Huang , Odin Zhang , Lirong Wu , Cheng Tan , Haitao Lin , Zhangyang Gao , Siyuan Li , Stan. Z. Li

Recent advances in de novo protein binder design have enabled increasing experimental validation, yet reported in silico metrics remain difficult to interpret or compare across studies due to non-standardized evaluation protocols. We…

Quantitative Methods · Quantitative Biology 2026-05-25 Cong Liu , Milong Ren , Jiaqi Guan , Chengyue Gong , Jinyuan Sun , Xinshi Chen , Wenzhi Xiao

Protein structure determination has long been one of the primary challenges of structural biology, to which deep machine learning (ML)-based approaches have increasingly been applied. However, these ML models generally do not incorporate…

Biological Physics · Physics 2025-11-14 Tom Pan , Evan Dramko , Mitchell D. Miller , Anastasios Kyrillidis , George N. Phillips
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