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Protein structure generative models excel at predicting single protein static structures from sequence, but routinely fail to capture the correct conformational state of protein complexes, critical for protein design and induced proximity…

Machine Learning · Computer Science 2026-05-27 Alon Shtrikman , Nitzan Simchi , Michal Ran Shchory , Sagie Brodsky , Eran Seger , Kirill Pevzner

After the recent ground-breaking advances in protein structure prediction, one of the remaining challenges in protein machine learning is to reliably predict distributions of structural states. Parametric models of fluctuations are…

Machine Learning · Computer Science 2024-01-25 Marloes Arts , Jes Frellsen , Wouter Boomsma

The paradigm that the primary amino acid sequence prescribes structure and thus function has for a long time been central to the understanding of protein science. Though the theory is supported by the behaviour of most structured proteins,…

Biological Physics · Physics 2022-12-19 Rickie Xian , Sarah Rauscher

Proteins are the fundamental macromolecules that play diverse and crucial roles in all living matter and have tremendous implications in healthcare, manufacturing, and biotechnology. Their functions are largely determined by the sequences…

Biomolecules · Quantitative Biology 2024-09-17 Boqiao Lai

Recent years have seen tremendous developments in the use of machine learning models to link amino acid sequence, structure and function of folded proteins. These methods are, however, rarely applicable to the wide range of proteins and…

Biomolecules · Quantitative Biology 2025-02-27 Sören von Bülow , Giulio Tesei , Kresten Lindorff-Larsen

Classification of proteins based on their structure provides a valuable resource for studying protein structure, function and evolutionary relationships. With the rapidly increasing number of known protein structures, manual and…

Computational Engineering, Finance, and Science · Computer Science 2009-07-14 Oktie Hassanzadeh

The interaction of a protein with its environment can be understood and controlled via its 3D structure. Experimental methods for protein structure determination, such as X-ray crystallography or cryogenic electron microscopy, shed light on…

Machine Learning · Computer Science 2025-04-24 Axel Levy , Eric R. Chan , Sara Fridovich-Keil , Frédéric Poitevin , Ellen D. Zhong , Gordon Wetzstein

Advances in manufacturing and characterization of complex molecular systems have created a need for new methods for design at molecular length scales. Emerging approaches are increasingly relying on the use of Artificial Intelligence (AI),…

Soft Condensed Matter · Physics 2022-08-17 Dan Mendels , Fabian Byléhn , Timothy W. Sirk , Juan J. de Pablo

Considering the significance of proteins, computational protein science has always been a critical scientific field, dedicated to revealing knowledge and developing applications within the protein sequence-structure-function paradigm. In…

Computational Engineering, Finance, and Science · Computer Science 2025-01-28 Wenqi Fan , Yi Zhou , Shijie Wang , Yuyao Yan , Hui Liu , Qian Zhao , Le Song , Qing Li

Mapping conformational heterogeneity of macromolecules presents a formidable challenge to X-ray crystallography and cryo-electron microscopy, which often presume its absence. This has severely limited our knowledge of the conformations…

Biological Physics · Physics 2015-05-14 P. Schwander , R. Fung , G. N. Phillips , A. Ourmazd

Proteins exist as a dynamic ensemble of multiple conformations, and these motions are often crucial for their functions. However, current structure prediction methods predominantly yield a single conformation, overlooking the conformational…

Biomolecules · Quantitative Biology 2025-06-18 Advaith Maddipatla , Nadav Bojan Sellam , Meital Bojan , Sanketh Vedula , Paul Schanda , Ailie Marx , Alex M. Bronstein

Motivation: Assessing the match between two biomolecular structures is at the heart of structural analyses such as superposition, alignment and docking. These tasks are typically solved with specialized structure-matching techniques…

Biomolecules · Quantitative Biology 2024-01-23 Michael Habeck , Andreas Kröpelin , Nima Vakili

High-throughput computational materials design promises to greatly accelerate the process of discovering new materials and compounds, and of optimizing their properties. The large databases of structures and properties that result from…

Chemical Physics · Physics 2016-11-22 Sandip De , Felix Musil , Teresa Ingram , Carsten Baldauf , Michele Ceriotti

As protein informatics advances rapidly, the demand for enhanced predictive accuracy, structural analysis, and functional understanding has intensified. Transformer models, as powerful deep learning architectures, have demonstrated…

Machine Learning · Computer Science 2025-05-28 Xiaowen Ling , Zhiqiang Li , Yanbin Wang , Zhuhong You

Structural dynamics of macromolecules is critical to their structural-function relationship. Cryogenic electron microscopy (CryoEM) provides snapshots of vitrified protein at different compositional and conformational states, and the…

Quantitative Methods · Quantitative Biology 2026-01-27 Muyuan Chen , Muchen Li , Renjie Liao

Bioinformatics has witnessed a paradigm shift with the increasing integration of artificial intelligence (AI), particularly through the adoption of foundation models (FMs). These AI techniques have rapidly advanced, addressing historical…

Quantitative Methods · Quantitative Biology 2024-02-08 Qing Li , Zhihang Hu , Yixuan Wang , Lei Li , Yimin Fan , Irwin King , Le Song , Yu Li

Cryo-electron tomography (cryo-ET) provides a unique window into molecular organization in cellular environments (in situ). However, the interpretation of molecular structural information is complicated by several intrinsic properties of…

Biomolecules · Quantitative Biology 2026-02-17 Slavica Jonic

The use of AI systems in healthcare for the early screening of diseases is of great clinical importance. Deep learning has shown great promise in medical imaging, but the reliability and trustworthiness of AI systems limit their deployment…

Image and Video Processing · Electrical Eng. & Systems 2023-05-17 Ke Zou , Zhihao Chen , Xuedong Yuan , Xiaojing Shen , Meng Wang , Huazhu Fu

New technologies have enabled the investigation of biology and human health at an unprecedented scale and in multiple dimensions. These dimensions include a myriad of properties describing genome, epigenome, transcriptome, microbiome,…

Quantitative Methods · Quantitative Biology 2018-10-22 Marinka Zitnik , Francis Nguyen , Bo Wang , Jure Leskovec , Anna Goldenberg , Michael M. Hoffman

The idea that structural disorder might be a novel mechanism of protein interaction is widespread in the Literature, although the number of statistically significant structural studies supporting this is surprisingly low. At variance with…

Disordered Systems and Neural Networks · Physics 2021-03-01 Beatriz Seoane , Alessandra Carbone