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Intrinsically disordered proteins (IDPs) constitute a broad set of proteins with few uniting and many diverging properties. IDPs-and intrinsically disordered regions (IDRs) interspersed between folded domains-are generally characterized as…

Biomolecules · Quantitative Biology 2021-06-03 Kresten Lindorff-Larsen , Birthe B. Kragelund

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

In 1999 Wright and Dyson highlighted the fact that large sections of the proteome of all organisms are comprised of protein sequences that lack globular folded structures under physiological conditions. Since then the biophysics community…

Biological Physics · Physics 2024-09-05 Zi Hao Liu , Maria Tsanai , Oufan Zhang , Julie Forman-Kay , Teresa Head-Gordon

We outline recent developments in artificial intelligence (AI) and machine learning (ML) techniques for integrative structural biology of intrinsically disordered proteins (IDP) ensembles. IDPs challenge the traditional protein…

Biomolecules · Quantitative Biology 2020-12-03 Arvind Ramanathan , Heng Ma , Akash Parvatikar , Chakra S. Chennubhotla

The human proteome is enriched in proteins that do not fold into a stable 3D structure. These intrinsically disordered proteins (IDPs) spontaneously fluctuate between a large number of configurations in their native form. Remarkably, the…

Although machine learning has transformed protein structure prediction of folded protein ground states with remarkable accuracy, intrinsically disordered proteins and regions (IDPs/IDRs) are defined by diverse and dynamical structural…

Biomolecules · Quantitative Biology 2025-04-01 Oufan Zhang , Zi Hao Liu , Julie D Forman-Kay , Teresa Head-Gordon

Recent advances in Language Models have enabled the protein modeling community with a powerful tool since protein sequences can be represented as text. Specifically, by taking advantage of Transformers, sequence-to-property prediction will…

Biomolecules · Quantitative Biology 2023-09-07 Chakradhar Guntuboina , Adrita Das , Parisa Mollaei , Seongwon Kim , Amir Barati Farimani

Intrinsically disordered regions (IDRs) account for one-third of the human proteome and play essential biological roles. However, predicting the functions of IDRs remains a major challenge due to their lack of stable structures, rapid…

Biomolecules · Quantitative Biology 2025-07-04 Đesika Kolarić , Chi Fung Willis Chow , Rita Zi Zhu , Agnes Toth-Petroczy , T. Reid Alderson , Iva Pritišanac

Intrinsically disordered proteins (IDPs) and multidomain proteins with flexible linkers show a high level of structural heterogeneity and are best described by ensembles consisting of multiple conformations with associated thermodynamic…

Biomolecules · Quantitative Biology 2021-12-13 F. Emil Thomasen , Kresten Lindorff-Larsen

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

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

In this paper we propose a straightforward operational definition of variants of disordered proteins, taking the human proteome as a case study. The focus is on a distinction between mostly unstructured proteins and proteins which contain…

Biomolecules · Quantitative Biology 2016-11-21 Antonio Deiana , Andrea Giansanti

Intrinsically disordered proteins are fascinating the community of protein science since the last decade, at least. There is a well-established line of research that intends to reveal the crucial role played by intrinsically disordered…

Biomolecules · Quantitative Biology 2014-10-17 Antonio Deiana , Andrea Giansanti

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

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

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…

It is well-known that intrinsically disordered proteins (IDP) are highly dynamic, which is related to their functionality in various biological processes. However, the characterization of the intricate structures of IDP has been a…

Biological Physics · Physics 2025-03-18 Danqi Lang , Le Chen , Jingyuan Li

We report simulation studies of 33 single intrinsically disordered proteins (IDPs) using coarse-grained (CG) bead-spring models where interactions among different amino acids are introduced through a hydropathy matrix and additional…

Soft Condensed Matter · Physics 2023-12-07 Swarnadeep Seth , Brandon Stine , Aniket Bhattacharya

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

Large pretrained language models have transformed natural language processing, and their adaptation to protein sequences -- viewed as strings of amino acid characters -- has advanced protein analysis. However, the distinct properties of…

Other Quantitative Biology · Quantitative Biology 2025-10-14 Sheikh Azizul Hakim , Kowshic Roy , M Saifur Rahman
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