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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

Intrinsically disordered proteins and regions are increasingly appreciated for their abundance in the proteome and the many functional roles they play in the cell. In this short review, we describe a variety of approaches used to obtain…

Biological Physics · Physics 2024-12-31 Zi Hao Liu , Maria Tsanai , Oufan Zhang , Teresa Head-Gordon , Julie Forman-Kay

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

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

Protein design has the potential to revolutionize biotechnology and medicine. While most efforts have focused on proteins with well-defined structures, increased recognition of the functional significance of intrinsically disordered…

Biomolecules · Quantitative Biology 2025-09-17 Giulio Tesei , Francesco Pesce , Kresten Lindorff-Larsen

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

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…

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

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

Intrinsically Disordered Proteins (IDPs) constitute a large and structure-less class of proteins with significant functions. The existence of IDPs challenges the conventional notion that the biological functions of proteins rely on their…

Biomolecules · Quantitative Biology 2024-11-26 Parisa Mollaei , Danush Sadasivam , Chakradhar Guntuboina , Amir Barati Farimani

Many pairwise additive force fields are in active use for intrinsically disordered proteins (IDPs) and regions (IDRs), some of which modify energetic terms to improve description of IDPs/IDRs, but are largely in disagreement with solution…

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

A significant part of the proteome is composed of intrinsically-disordered proteins (IDPs). These proteins do not fold into a well-defined structure and behave like ordinary polymers. In this work we consider IDPs which have the tendency to…

Biological Physics · Physics 2018-03-14 Dino Osmanovic , Yitzhak Rabin

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

The DisProt database is a significant resource containing manually curated data on experimentally validated intrinsically disordered proteins (IDPs) and regions (IDRs) from the literature. Developed in 2005, its primary goal was to collect…

Intrinsically disordered protein regions (IDRs) are found across all domains of life and are characterized by a lack of stable 3D structure. Nevertheless, IDRs play critical roles in the most tightly regulated cellular processes, including…

Biomolecules · Quantitative Biology 2025-08-27 Emery T. Usher , Jacqueline F. Pelham

Intrinsically disordered proteins (IDPs) do not possess well-defined three-dimensional structures in solution under physiological conditions. We develop all-atom, united-atom, and coarse-grained Langevin dynamics simulations for the IDP…

Complexes of physically interacting proteins constitute fundamental functional units responsible for driving biological processes within cells. A faithful reconstruction of the entire set of complexes is therefore essential to understand…

Molecular Networks · Quantitative Biology 2015-05-21 Sriganesh Srihari , Chern Han Yong , Ashwini Patil , Limsoon Wong

Protein folding produces characteristic and functional three-dimensional structures from unfolded polypeptides or disordered coils. The emergence of extraordinary complexity in the protein folding process poses astonishing challenges to…

Biomolecules · Quantitative Biology 2013-08-14 Kelin Xia , Guo-Wei Wei

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…

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