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Disordered proteins play essential roles in myriad cellular processes, yet their structural characterization remains a major challenge due to their dynamic and heterogeneous nature. We here present a community-driven initiative to address…

Despite significant progress in static protein structure collection and prediction, the dynamic behavior of proteins, one of their most vital characteristics, has been largely overlooked in prior research. This oversight can be attributed…

Biomolecules · Quantitative Biology 2024-09-19 Ce Liu , Jun Wang , Zhiqiang Cai , Yingxu Wang , Huizhen Kuang , Kaihui Cheng , Liwei Zhang , Qingkun Su , Yining Tang , Fenglei Cao , Limei Han , Siyu Zhu , Yuan Qi

Advances in deep learning have opened an era of abundant and accurate predicted protein structures; however, similar progress in protein ensembles has remained elusive. This review highlights several recent research directions towards…

Biomolecules · Quantitative Biology 2025-09-23 Bowen Jing , Bonnie Berger , Tommi Jaakkola

Recent advances in generative models, particularly diffusion and auto-regressive models, have revolutionized fields like computer vision and natural language processing. However, their application to structure-based drug design (SBDD)…

Machine Learning · Computer Science 2025-07-29 Yi He , Ailun Wang , Zhi Wang , Yu Liu , Xingyuan Xu , Wen Yan

Recent advances in geometric deep learning and generative modeling have enabled the design of novel proteins with a wide range of desired properties. However, current state-of-the-art approaches are typically restricted to generating…

Biomolecules · Quantitative Biology 2025-08-26 Vsevolod Viliuga , Leif Seute , Nicolas Wolf , Simon Wagner , Arne Elofsson , Jan Stühmer , Frauke Gräter

We propose generative neural network methods to generate DNA sequences and tune them to have desired properties. We present three approaches: creating synthetic DNA sequences using a generative adversarial network; a DNA-based variant of…

Machine Learning · Computer Science 2017-12-19 Nathan Killoran , Leo J. Lee , Andrew Delong , David Duvenaud , Brendan J. Frey

Protein dynamics play a crucial role in protein biological functions and properties, and their traditional study typically relies on time-consuming molecular dynamics (MD) simulations conducted in silico. Recent advances in generative…

Biomolecules · Quantitative Biology 2025-06-02 Jiarui Lu , Xiaoyin Chen , Stephen Zhewen Lu , Aurélie Lozano , Vijil Chenthamarakshan , Payel Das , Jian Tang

The structure of a protein is crucial in determining its functionality, and is much more conserved than sequence during evolution. A key task in structural biology is to compare protein structures in order to determine evolutionary…

Methodology · Statistics 2019-11-06 Christopher Fallaize , Peter Green , Kanti Mardia , Stuart Barber

Protein sequence generation for engineering requires samples that are biophysically plausible and, when targeting a family/domain, remain recognizable members while exploring within-family diversity. Current discrete generative models…

Computational Engineering, Finance, and Science · Computer Science 2026-05-25 Langzhang Liang , Ming Yang , Yi Feng , Junfan Li , Shirui Pan , Yinghui Xu , Tianlei Ying , Yizhen Zheng , Zenglin Xu

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

Neural networks that incorporate geometric relationships respecting SE(3) group transformations (e.g. rotations and translations) are increasingly important in molecular applications, such as molecular property prediction, protein structure…

Machine Learning · Computer Science 2025-10-21 Jose Siguenza , Bharath Ramsundar

Generating molecules that bind to specific proteins is an important but challenging task in drug discovery. Previous works usually generate atoms in an auto-regressive way, where element types and 3D coordinates of atoms are generated one…

Biomolecules · Quantitative Biology 2024-07-16 Haitao Lin , Yufei Huang , Odin Zhang , Siqi Ma , Meng Liu , Xuanjing Li , Lirong Wu , Jishui Wang , Tingjun Hou , Stan Z. Li

Classifying protein topology is essential for deciphering biological function, but progress is held back by the lack of large-scale benchmarks that avoid duplicates and by models that do not scale well. We introduce TEDBench, a large-scale,…

Machine Learning · Computer Science 2026-05-19 Dexiong Chen , Andrei Manolache , Mathias Niepert , Karsten Borgwardt

Learning from 3D protein structures has gained wide interest in protein modeling and structural bioinformatics. Unfortunately, the number of available structures is orders of magnitude lower than the training data sizes commonly used in…

Biomolecules · Quantitative Biology 2022-06-01 Pedro Hermosilla , Timo Ropinski

Molecular structure generation is a fundamental problem that involves determining the 3D positions of molecules' constituents. It has crucial biological applications, such as molecular docking, protein folding, and molecular design. Recent…

Machine Learning · Computer Science 2025-08-27 Wenyin Zhou , Christopher Iliffe Sprague , Vsevolod Viliuga , Matteo Tadiello , Arne Elofsson , Hossein Azizpour

Proteins are macromolecules that perform essential functions in all living organisms. Designing novel proteins with specific structures and desired functions has been a long-standing challenge in the field of bioengineering. Existing…

Biomolecules · Quantitative Biology 2023-03-03 Chence Shi , Chuanrui Wang , Jiarui Lu , Bozitao Zhong , Jian Tang

Computational protein design has the potential to deliver novel molecular structures, binders, and catalysts for myriad applications. Recent neural graph-based models that use backbone coordinate-derived features show exceptional…

Biomolecules · Quantitative Biology 2022-04-28 Alex J. Li , Vikram Sundar , Gevorg Grigoryan , Amy E. Keating

Rapid progress in deep learning has spurred its application to bioinformatics problems including protein structure prediction and design. In classic machine learning problems like computer vision, progress has been driven by standardized…

Biomolecules · Quantitative Biology 2019-02-04 Mohammed AlQuraishi

Protein generative models have shown remarkable promise in protein design, yet their success rates remain constrained by reliance on curated sequence-structure datasets and by misalignment between supervised objectives and real design…

Machine Learning · Computer Science 2026-03-03 Ziwen Wang , Jiajun Fan , Ruihan Guo , Thao Nguyen , Heng Ji , Ge Liu

The grand challenge of protein engineering is the development of computational models that can characterize and generate protein sequences for any arbitrary function. However, progress today is limited by lack of 1) benchmarks with which to…

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