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Intrinsically disordered proteins (IDPs) are important for biological functions. In contrast to folded proteins, molecular recognition among certain IDPs is "fuzzy" in that their binding and/or phase separation are stochastically governed…

Biomolecules · Quantitative Biology 2020-08-10 Alan N. Amin , Yi-Hsuan Lin , Suman Das , Hue Sun Chan

Intrinsically disordered regions (IDRs) play central roles in cellular function, yet remain poorly evaluated by existing protein structure prediction benchmarks. Current evaluations largely focus on well-folded domains, overlooking three…

Biomolecules · Quantitative Biology 2026-02-11 Xinyue Zeng , Tuo Wang , Adithya Kulkarni , Alexander Lu , Alexandra Ni , Phoebe Xing , Junhan Zhao , Siwei Chen , Dawei Zhou

Intrinsically disordered regions (IDRs) of proteins mediate sequence-specific interactions underlying diverse cellular processes, including the formation of biomolecular condensates. Although IDRs strongly influence condensate compositions,…

Soft Condensed Matter · Physics 2026-03-10 Zhuang Liu , Beijia Yuan , Mihir Rao , Gautam Reddy , William M. Jacobs

Short-range interactions and long-range contacts drive the 3D folding of structured proteins. The proteins' structure has a direct impact on their biological function. However, nearly 40% of the eukaryotes proteome is composed of…

All-atom molecular dynamics (MD) computer simulations are a valuable tool for characterizing the conformational ensembles of intrinsically disordered proteins (IDPs). IDP conformational ensembles are highly heterogeneous and contain…

Chemical Physics · Physics 2025-05-06 Jaya Krishna Koneru , Korey M. Reid , Paul Robustelli

Integrative modeling enables structure determination for large macromolecular assemblies by combining data from multiple sources of experiment data with theoretical and computational predictions. Recent advancements in AI-based structure…

Biomolecules · Quantitative Biology 2025-01-24 Kartik Majila , Shreyas Arvindekar , Muskaan Jindal , Shruthi Viswanath

Proteins play crucial roles in every cellular process by interacting with each other, with nucleic acids, metabolites, and other molecules. The resulting assemblies can be very large and intricate and pose challenges to experimental…

Biomolecules · Quantitative Biology 2021-03-16 Charlotte W. van Noort , Rodrigo V. Honorato , Alexandre M. J. J. Bonvin

Complexes of physically interacting proteins are one of the fundamental functional units responsible for driving key biological mechanisms within the cell. Their identification is therefore necessary not only to understand complex formation…

Computational Engineering, Finance, and Science · Computer Science 2012-11-27 Sriganesh Srihari , Hon Wai Leong

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

An intrinsically disordered protein (IDP) lacks a stable three-dimensional structure, while it folds into a specific structure when it binds to a target molecule. In some IDP-target complexes, not all target binding surfaces are exposed on…

Biomolecules · Quantitative Biology 2013-12-12 Nobu C. Shirai , Macoto Kikuchi

Understanding and predicting the phase behavior of intrinsically disordered proteins (IDPs) is of significant interest due to their role in many biological processes. However, effectively characterizing phase behavior and its complex…

Soft Condensed Matter · Physics 2025-07-18 Wesley W. Oliver , William M. Jacobs , Michael A. Webb

Accurate protein structural ensembles can be determined with metainference, a Bayesian inference method that integrates experimental information with prior knowledge of the system and deals with all sources of uncertainty and errors as well…

Quantitative Methods · Quantitative Biology 2019-01-24 Thomas Löhr , Carlo Camilloni , Massimiliano Bonomi , Michele Vendruscolo

Liquid-liquid phase separation is the mechanism underlying the formation of biomolecular condensates. Disordered protein regions often drive phase separation, but molecular interactions of disordered protein regions are not well understood,…

Biomolecules · Quantitative Biology 2020-08-10 Wade Borcherds , Anne Bremer , Madeleine B. Borgia , Tanja Mittag

Intrinsically Disordered Proteins (IDPs) perform a broad range of biological functions. Their relevance has motivated intense research activity seeking to characterize their sequence/structure/function relationships. However, the…

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

Despite many advances in computational modeling of protein structures, these methods have not been widely utilized by experimental structural biologists. Two major obstacles are preventing the transition from a purely-experimental to a…

Biomolecules · Quantitative Biology 2019-11-04 Rishi Mukhopadhyay , Paul Shealy , Homayoun Valafar

Proteins are biomolecules of life. They fold into a great variety of three-dimensional (3D) shapes. Underlying these folding patterns are many recurrent structural fragments or building blocks (analogous to `LEGO bricks'). This paper…

Quantitative Methods · Quantitative Biology 2013-10-08 Arun S. Konagurthu , Arthur M. Lesk , David Abramson , Peter J. Stuckey , Lloyd Allison

While deep learning has revolutionized the prediction of rigid protein structures, modelling the conformational ensembles of Intrinsically Disordered Proteins (IDPs) remains a key frontier. Current AI paradigms present a trade-off: Protein…

Biomolecules · Quantitative Biology 2025-12-19 Eoin Quinn , Marco Carobene , Jean Quentin , Sebastien Boyer , Miguel Arbesú , Oliver Bent

Intrinsically disordered proteins (IDPs) play a significant role in intracellular phenomena and are known to exist in an ensemble of inter-converting conformations in solution. Accurately modeling the conformations of IDPs in solution poses…

Biological Physics · Physics 2025-08-27 Rohan S. Adhikari , Winnie H. Shi , Amanda B. Marciel , Walter G. Chapman

Proteins are sequences of amino acids that serve as the basic building blocks of living organisms. Despite rapidly growing databases documenting structural and functional information for various protein sequences, our understanding of…

Biomolecules · Quantitative Biology 2025-01-06 Weihang Dai