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individual proteins and regulated protein turnover. Often, post-translational modifications such as phosphorylation tune the affinity (not rarely by several orders of magnitude) of individual linear motifs for specific interactions. Relatively rapid evolution and a relatively small number of structural restraints for establishing novel (low-affinity) interfaces make it particularly challenging to detect linear motifs but their widespread biological roles and the fact that many viruses mimick/hijack linear motifs to efficiently recode infected cells underlines the timely urgency of research on this very challenging and exciting topic.
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characterized as disorder-promoting amino acids, while order-promoting amino acids W, C, F, I, Y, V, L, and N are hydrophobic and uncharged. The remaining amino acids H, M, T and D are ambiguous, found in both ordered and unstructured regions. A more recent analysis ranked amino acids by their propensity to form disordered regions as follows (order promoting to disorder promoting): W, F, Y, I, M, L, V, N, C, T, A, G, R, D, H, Q, K, S, E, P. As it can be seen from the list, small, charged, hydrophilic residues often promote disorder, while large and hydrophobic residues promote order.
306:). The coupled folding and binding may be local, involving only a few interacting residues, or it might involve an entire protein domain. It was recently shown that the coupled folding and binding allows the burial of a large surface area that would be possible only for fully structured proteins if they were much larger. Moreover, certain disordered regions might serve as "molecular switches" in regulating certain biological function by switching to ordered conformation upon molecular recognition like small molecule-binding, DNA/RNA binding, ion interactions etc.
378:). Many disordered proteins reveal regions without any regular secondary structure. These regions can be termed as flexible, compared to structured loops. While the latter are rigid and contain only one set of Ramachandran angles, IDPs involve multiple sets of angles. The term flexibility is also used for well-structured proteins, but describes a different phenomenon in the context of disordered proteins. Flexibility in structured proteins is bound to an equilibrium state, while it is not so in IDPs. Many disordered proteins also reveal
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for accurate representation of these ensembles by computer simulations. All-atom molecular dynamic simulations can be used for this purpose but their use is limited by the accuracy of current force-fields in representing disordered proteins. Nevertheless, some force-fields have been explicitly developed for studying disordered proteins by optimising force-field parameters using available NMR data for disordered proteins. (examples are CHARMM 22*, CHARMM 32, Amber ff03* etc.)
20:
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the expense of IDP determination. In order to overcome this obstacle, computer-based methods are created for predicting protein structure and function. It is one of the main goals of bioinformatics to derive knowledge by prediction. Predictors for IDP function are also being developed, but mainly use structural information such as
244:, thus it has been proposed that the flexibility of disordered proteins facilitates the different conformational requirements for binding the modifying enzymes as well as their receptors. Intrinsic disorder is particularly enriched in proteins implicated in cell signaling and transcription, as well as
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is thought to be responsible. The structural flexibility of this protein together with its susceptibility to modification in the cell leads to misfolding and aggregation. Genetics, oxidative and nitrative stress as well as mitochondrial impairment impact the structural flexibility of the unstructured
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Many computational methods exploit sequence information to predict whether a protein is disordered. Notable examples of such software include IUPRED and
Disopred. Different methods may use different definitions of disorder. Meta-predictors show a new concept, combining different primary predictors to
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suggested that the systematic conformational search of a long polypeptide is unlikely to yield a single folded protein structure on biologically relevant timescales (i.e. microseconds to minutes). Curiously, for many (small) proteins or protein domains, relatively rapid and efficient refolding can be
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Owing to high structural heterogeneity, NMR/SAXS experimental parameters obtained will be an average over a large number of highly diverse and disordered states (an ensemble of disordered states). Hence, to understand the structural implications of these experimental parameters, there is a necessity
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Determining disordered regions from biochemical methods is very costly and time-consuming. Due to the variable nature of IDPs, only certain aspects of their structure can be detected, so that a full characterization requires a large number of different methods and experiments. This further increases
365:
Therefore, their structures are strongly function-related. However, only few proteins are fully disordered in their native state. Disorder is mostly found in intrinsically disordered regions (IDRs) within an otherwise well-structured protein. The term intrinsically disordered protein (IDP) therefore
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This information is the basis of most sequence-based predictors. Regions with little to no secondary structure, also known as NORS (NO Regular
Secondary structure) regions, and low-complexity regions can easily be detected. However, not all disordered proteins contain such low complexity sequences.
293:
Unlike globular proteins, IDPs do not have spatially-disposed active pockets. Fascinatingly, 80% of target-unbound IDPs (~4 dozens) subjected to detailed structural characterization by NMR possess linear motifs termed PresMos (pre-structured motifs) that are transient secondary structural elements
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Separating disordered from ordered proteins is essential for disorder prediction. One of the first steps to find a factor that distinguishes IDPs from non-IDPs is to specify biases within the amino acid composition. The following hydrophilic, charged amino acids A, R, G, Q, S, P, E and K have been
353:
of the complex is modulated via post-translational modifications or protein interactions. Specificity of DNA binding proteins often depends on the length of fuzzy regions, which is varied by alternative splicing. Some fuzzy complexes may exhibit high binding affinity, although other studies showed
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and toxicity as those proteins start binding to each other randomly and can lead to cancer or cardiovascular diseases. Thereby, misfolding can happen spontaneously because millions of copies of proteins are made during the lifetime of an organism. The aggregation of the intrinsically unstructured
162:
in that the amino acid sequence of a protein determines its structure which, in turn, determines its function. In 1950, Karush wrote about 'Configurational
Adaptability' contradicting this assumption. He was convinced that proteins have more than one configuration at the same energy level and can
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for visualising molecular interactions and conformational transitions, x-ray crystallography to highlight more mobile regions in otherwise rigid protein crystals, cryo-EM to reveal less fixed parts of proteins, light scattering to monitor size distributions of IDPs or their aggregation kinetics,
522:
have been introduced, which allow to determine the fraction folded/disordered without the need for purification. Even subtle differences in the stability of missense mutations, protein partner binding and (self)polymerisation-induced folding of (e.g.) coiled-coils can be detected using FASTpp as
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have large intrinsically unstructured regions, for example p53 and BRCA1. These regions of the proteins are responsible for mediating many of their interactions. Taking the cell's native defense mechanisms as a model drugs can be developed, trying to block the place of noxious substrates and
373:
amino acids and a high proportion of polar and charged amino acids, usually referred to as low hydrophobicity. This property leads to good interactions with water. Furthermore, high net charges promote disorder because of electrostatic repulsion resulting from equally charged residues. Thus
284:
Linear motifs are short disordered segments of proteins that mediate functional interactions with other proteins or other biomolecules (RNA, DNA, sugars etc.). Many roles of linear motifs are associated with cell regulation, for instance in control of cell shape, subcellular localisation of
204:
It is now generally accepted that proteins exist as an ensemble of similar structures with some regions more constrained than others. IDPs occupy the extreme end of this spectrum of flexibility and include proteins of considerable local structure tendency or flexible multidomain assemblies.
172:
from 1973, the fixed 3D structure of these proteins is uniquely encoded in its primary structure (the amino acid sequence), is kinetically accessible and stable under a range of (near) physiological conditions, and can therefore be considered as the native state of such "ordered" proteins.
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MD simulations restrained by experimental parameters (restrained-MD) have also been used to characterise disordered proteins. In principle, one can sample the whole conformational space given an MD simulation (with accurate Force-field) is run long enough. Because of very high structural
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can predict
Intrinsic Disorder (ID) propensity with high accuracy (approaching around 80%) based on primary sequence composition, similarity to unassigned segments in protein x-ray datasets, flexible regions in NMR studies and physico-chemical properties of amino acids.
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Dunker AK, Lawson JD, Brown CJ, Williams RM, Romero P, Oh JS, Oldfield CJ, Campen AM, Ratliff CM, Hipps KW, Ausio J, Nissen MS, Reeves R, Kang C, Kissinger CR, Bailey RW, Griswold MD, Chiu W, Garner EC, Obradovic Z (2001-01-01). "Intrinsically disordered protein".
374:
disordered sequences cannot sufficiently bury a hydrophobic core to fold into stable globular proteins. In some cases, hydrophobic clusters in disordered sequences provide the clues for identifying the regions that undergo coupled folding and binding (refer to
848:
Dunker AK, Lawson JD, Brown CJ, Williams RM, Romero P, Oh JS, Oldfield CJ, Campen AM, Ratliff CM, Hipps KW, Ausio J, Nissen MS, Reeves R, Kang C, Kissinger CR, Bailey RW, Griswold MD, Chiu W, Garner EC, Obradovic Z (2001). "Intrinsically disordered protein".
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recently demonstrated using the tropomyosin-troponin protein interaction. Fully unstructured protein regions can be experimentally validated by their hypersusceptibility to proteolysis using short digestion times and low protease concentrations.
187:
In 2001, Dunker questioned whether the newly found information was ignored for 50 years with more quantitative analyses becoming available in the 2000s. In the 2010s it became clear that IDPs are common among disease-related proteins, such as
294:
primed for target recognition. In several cases it has been demonstrated that these transient structures become full and stable secondary structures, e.g., helices, upon target binding. Hence, PresMos are the putative active sites in IDPs.
557:
for high-resolution insights into the ensembles of IDPs and their oligomers or aggregates, nanopores to reveal global shape distributions of IDPs, magnetic tweezers to study structural transitions for long times at low forces, high-speed
31:). The central part shows relatively ordered structure. Conversely, the N- and C-terminal regions (left and right, respectively) show βintrinsic disorderβ, although a short helical region persists in the N-terminal tail. Ten alternative
386:. While low complexity sequences are a strong indication of disorder, the reverse is not necessarily true, that is, not all disordered proteins have low complexity sequences. Disordered proteins have a low content of predicted
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Moreover, various protocols and methods of analyzing IDPs, such as studies based on quantitative analysis of GC content in genes and their respective chromosomal bands, have been used to understand functional IDP segments.
3707:
Iida S, Kawabata T, Kasahara K, Nakamura H, Higo J (April 2019). "Multimodal
Structural Distribution of the p53 C-Terminal Domain upon Binding to S100B via a Generalized Ensemble Method: From Disorder to Extradisorder".
122:. Many IDPs can also adopt a fixed three-dimensional structure after binding to other macromolecules. Overall, IDPs are different from structured proteins in many ways and tend to have distinctive function, structure,
3614:
Zerze GH, Miller CM, Granata D, Mittal J (June 2015). "Free energy surface of an intrinsically disordered protein: comparison between temperature replica exchange molecular dynamics and bias-exchange metadynamics".
397:
has been applied to track the dynamics of disordered protein domains. By employing a topological approach, one can categorize motifs according to their topological buildup and the timescale of their formation.
613:
is a database combining experimentally curated disorder annotations (e.g. from DisProt) with data derived from missing residues in X-ray crystallographic structures and flexible regions in NMR structures.
2856:
Japrung D, Dogan J, Freedman KJ, Nadzeyka A, Bauerdick S, Albrecht T, Kim MJ, Jemth P, Edel JB (February 2013). "Single-molecule studies of intrinsically disordered proteins using solid-state nanopores".
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heterogeneity, the time scales that needs to be run for this purpose are very large and are limited by computational power. However, other computational techniques such as accelerated-MD simulations,
224:. Based on DISOPRED2 prediction, long (>30 residue) disordered segments occur in 2.0% of archaean, 4.2% of eubacterial and 33.0% of eukaryotic proteins, including certain disease-related proteins.
406:
IDPs can be validated in several contexts. Most approaches for experimental validation of IDPs are restricted to extracted or purified proteins while some new experimental strategies aim to explore
2949:
Miyagi A, Tsunaka Y, Uchihashi T, Mayanagi K, Hirose S, Morikawa K, Ando T (September 2008). "Visualization of intrinsically disordered regions of proteins by high-speed atomic force microscopy".
345:
Intrinsically disordered proteins can retain their conformational freedom even when they bind specifically to other proteins. The structural disorder in bound state can be static or dynamic. In
712:. The globular thioredoxin fold is depicted in blue, while the disordered N-tail in green. According to the MD results, the disordered tail can be modulating the dynamics of the binding pocket.
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106:
IDPs are a very large and functionally important class of proteins and their discovery has disproved the idea that three-dimensional structures of proteins must be fixed to accomplish their
451:
Intrinsically unfolded proteins, once purified, can be identified by various experimental methods. The primary method to obtain information on disordered regions of a protein is
3246:
Balatti GE, Barletta GP, Parisi G, Tosatto SC, Bellanda M, Fernandez-Alberti S (December 2021). "Intrinsically
Disordered Region Modulates Ligand Binding in Glutaredoxin 1 from
176:
During the subsequent decades, however, many large protein regions could not be assigned in x-ray datasets, indicating that they occupy multiple positions, which average out in
3837:
Garaizar A, Espinosa JR (September 2021). "Salt dependent phase behavior of intrinsically disordered proteins from a coarse-grained model with explicit water and ions".
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Apicella A, Marascio M, Colangelo V, Soncini M, Gautieri A, Plummer CJ (June 2017). "Molecular dynamics simulations of the intrinsically disordered protein amelogenin".
1321:
Ward JJ, Sodhi JS, McGuffin LJ, Buxton BF, Jones DT (March 2004). "Prediction and functional analysis of native disorder in proteins from the three kingdoms of life".
260:
Disordered regions are often found as flexible linkers or loops connecting domains. Linker sequences vary greatly in length but are typically rich in polar uncharged
2230:
Borgia A, Borgia MB, Bugge K, Kissling VM, Heidarsson PO, Fernandes CB, Sottini A, Soranno A, Buholzer KJ, Nettels D, Kragelund BB, Best RB, Schuler B (March 2018).
309:
The ability of disordered proteins to bind, and thus to exert a function, shows that stability is not a required condition. Many short functional sites, for example
2668:
Robaszkiewicz K, Ostrowska Z, Cyranka-Czaja A, Moraczewska J (May 2015). "Impaired tropomyosin-troponin interactions reduce activation of the actin thin filament".
1906:
Lee SH, Kim DH, Han JJ, Cha EJ, Lim JE, Cho YJ, Lee C, Han KH (February 2012). "Understanding pre-structured motifs (PresMos) in intrinsically unfolded proteins".
393:
Due to the disordered nature of these proteins, topological approaches have been developed to search for conformational patterns in their dynamics. For instance,
3751:
Kurcinski M, Kolinski A, Kmiecik S (June 2014). "Mechanism of
Folding and Binding of an Intrinsically Disordered Protein As Revealed by ab Initio Simulations".
3295:"Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone Ο, Ο and side-chain Ο(1) and Ο(2) dihedral angles"
362:
Intrinsically disordered proteins adapt many different structures in vivo according to the cell's conditions, creating a structural or conformational ensemble.
2420:
Scalvini B. et al., Circuit
Topology Approach for the Comparative Analysis of Intrinsically Disordered Proteins. J. Chem. Inf. Model. 63, 8, 2586β2602 (2023)
181:
32:
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Mohan A, Oldfield CJ, Radivojac P, Vacic V, Cortese MS, Dunker AK, Uversky VN (October 2006). "Analysis of molecular recognition features (MoRFs)".
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persistence of intrinsic disorder has been achieved by in-cell NMR upon electroporation of a purified IDP and recovery of cells to an intact state.
2103:
Atkinson SC, Audsley MD, Lieu KG, Marsh GA, Thomas DR, Heaton SM, Paxman JJ, Wagstaff KM, Buckle AM, Moseley GW, Jans DA, Borg NA (January 2018).
1610:
Iakoucheva LM, Brown CJ, Lawson JD, ObradoviΔ Z, Dunker AK (October 2002). "Intrinsic disorder in cell-signaling and cancer-associated proteins".
1560:"Phosphoproteomic analysis of the mouse brain cytosol reveals a predominance of protein phosphorylation in regions of intrinsic sequence disorder"
3033:
Schlessinger A, Schaefer C, Vicedo E, Schmidberger M, Punta M, Rost B (June 2011). "Protein disorder--a breakthrough invention of evolution?".
369:
The existence and kind of protein disorder is encoded in its amino acid sequence. In general, IDPs are characterized by a low content of bulky
2625:
Park C, Marqusee S (March 2005). "Pulse proteolysis: a simple method for quantitative determination of protein stability and ligand binding".
333:. This enables such viruses to overcome their informationally limited genomes by facilitating binding, and manipulation of, a large number of
1976:
Gunasekaran K, Tsai CJ, Kumar S, Zanuy D, Nussinov R (February 2003). "Extended disordered proteins: targeting function with less scaffold".
553:
Single-molecule methods to study IDPs include spFRET to study conformational flexibility of IDPs and the kinetics of structural transitions,
3148:"Structures of the E46K mutant-type Ξ±-synuclein protein and impact of E46K mutation on the structures of the wild-type Ξ±-synuclein protein"
2289:"Binding Affinity and Function of the Extremely Disordered Protein Complex Containing Human Linker Histone H1.0 and Its Chaperone ProTΞ±"
657:
Due to the different approaches of predicting disordered proteins, estimating their relative accuracy is fairly difficult. For example,
2431:
Theillet FX, Binolfi A, Bekei B, Martorana A, Rose HM, Stuiver M, Verzini S, Lorenz D, van Rossum M, Goldfarb D, Selenko P (2016).
739:
representation with implicit and explicit solvents have been used to sample broader conformational space in smaller time scales.
1027:
Mir M, Stadler MR, Ortiz SA, Hannon CE, Harrison MM, Darzacq X, Eisen MB (December 2018). Singer RH, Struhl K, Crocker J (eds.).
4031:
609:
database contains a collection of manually curated protein segments which have been experimentally determined to be disordered.
584:, human growth hormone bound to receptor). Compilation of screenshots from PDB database and molecule representation via
1371:
Uversky VN, Oldfield CJ, Dunker AK (2008). "Intrinsically disordered proteins in human diseases: introducing the D2 concept".
410:
conformations and structural variations of IDPs inside intact living cells and systematic comparisons between their dynamics
636:
593:
349:
structural multiplicity is required for function and the manipulation of the bound disordered region changes activity. The
313:
are over-represented in disordered proteins. Disordered proteins and short linear motifs are particularly abundant in many
2705:"Large extent of disorder in Adenomatous Polyposis Coli offers a strategy to guard Wnt signalling against point mutations"
180:
maps. The lack of fixed, unique positions relative to the crystal lattice suggested that these regions were "disordered".
943:
Dunker AK, Silman I, Uversky VN, Sussman JL (December 2008). "Function and structure of inherently disordered proteins".
518:. (Folded proteins typically show dispersions as large as 5 ppm for the amide protons.) Recently, new methods including
479:
265:
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experiment that is designed to test methods according accuracy in finding regions with missing 3D structure (marked in
519:
379:
159:
3788:"Modeling of Disordered Protein Structures Using Monte Carlo Simulations and Knowledge-Based Statistical Force Fields"
3103:
Ferron F, Longhi S, Canard B, Karlin D (October 2006). "A practical overview of protein disorder prediction methods".
1428:
825:
276:. The flexible linker of FBP25 which connects two domains of FKBP25 is important for the binding of FKBP25 with DNA.
3342:
Best RB (February 2017). "Computational and theoretical advances in studies of intrinsically disordered proteins".
2894:"Mechanical unzipping and rezipping of a single SNARE complex reveals hysteresis as a force-generating mechanism"
2385:
Oldfield CJ, Dunker AK (2014). "Intrinsically disordered proteins and intrinsically disordered protein regions".
666:
592:
Intrinsic disorder can be either annotated from experimental information or predicted with specialized software.
264:. Flexible linkers allow the connecting domains to freely twist and rotate to recruit their binding partners via
241:
4087:
570:
475:
330:
2517:"Biotin proximity tagging favours unfolded proteins and enables the study of intrinsically disordered regions"
1182:"Micelle-induced folding of spinach thylakoid soluble phosphoprotein of 9 kDa and its functional implications"
252:
tend to have higher disorder. In animals, genes with high disorder are lost at higher rates during evolution.
2762:
Brucale M, Schuler B, Samorì B (March 2014). "Single-molecule studies of intrinsically disordered proteins".
471:
142:
of NMR structures of the
Thylakoid soluble phosphoprotein TSP9, which shows a largely flexible protein chain.
1859:"Structural basis of nucleic acid recognition by FK506-binding protein 25 (FKBP25), a nuclear immunophilin"
232:
Highly dynamic disordered regions of proteins have been linked to functionally important phenomena such as
158:
might be generally required to mediate biological functions of proteins. These publications solidified the
3652:"The inverted free energy landscape of an intrinsically disordered peptide by simulations and experiments"
2195:
Fuxreiter M, Simon I, Bondos S (August 2011). "Dynamic protein-DNA recognition: beyond what can be seen".
302:
Many unstructured proteins undergo transitions to more ordered states upon binding to their targets (e.g.
208:
Intrinsic disorder is particularly elevated among proteins that regulate chromatin and transcription, and
184:
also demonstrated the presence of large flexible linkers and termini in many solved structural ensembles.
155:
507:
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Folded proteins have a high density (partial specific volume of 0.72-0.74 mL/g) and commensurately small
2424:
1655:
Sandhu KS (2009). "Intrinsic disorder explains diverse nuclear roles of chromatin remodeling proteins".
1411:
Bu Z, Callaway DJ (2011). "Proteins MOVE! Protein dynamics and long-range allostery in cell signaling".
4092:
3650:
Granata D, Baftizadeh F, Habchi J, Galvagnion C, De Simone A, Camilloni C, et al. (October 2015).
3377:
Chong SH, Chatterjee P, Ham S (May 2017). "Computer
Simulations of Intrinsically Disordered Proteins".
605:
Databases have been established to annotate protein sequences with intrinsic disorder information. The
466:. Hence, unfolded proteins can be detected by methods that are sensitive to molecular size, density or
221:
64:
2105:"Recognition by host nuclear transport proteins drives disorder-to-order transition in Hendra virus V"
2799:"Diverse metastable structures formed by small oligomers of Ξ±-synuclein probed by force spectroscopy"
802:
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123:
3998:
1335:
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1457:"At the dawn of the 21st century: Is dynamics the missing link for understanding enzyme catalysis?"
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van der Lee R, Buljan M, Lang B, Weatheritt RJ, Daughdrill GW, Dunker AK, et al. (July 2014).
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Intrinsically unstructured proteins have been implicated in a number of diseases. Aggregation of
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are often trained on different datasets. The disorder prediction category is a part of biannual
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588:. Blue and red arrows point to missing residues on receptor and growth hormone, respectively.
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2011:
Sandhu KS, Dash D (July 2007). "Dynamic alpha-helices: conformations that do not conform".
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3457:"Multiscale ensemble modeling of intrinsically disordered proteins: p53 N-terminal domain"
2568:"Determining biophysical protein stability in lysates by a fast proteolysis assay, FASTpp"
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8:
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REMARK465 - missing electron densities in X-ray structure representing protein disorder (
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1415:. Advances in Protein Chemistry and Structural Biology. Vol. 83. pp. 163β221.
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3890:"Digested disorder: Quarterly intrinsic disorder digest (January/February/March, 2013)"
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240:. Many disordered proteins have the binding affinity with their receptors regulated by
3939:"Genealogy of an ancient protein family: the Sirtuins, a family of disordered members"
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1989:
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Ciemny MP, Badaczewska-Dawid AE, Pikuzinska M, Kolinski A, Kmiecik S (January 2019).
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1810:"Differential Retention of Pfam Domains Contributes to Long-term Evolutionary Trends"
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1029:"Dynamic multifactor hubs interact transiently with sites of active transcription in
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914:
897:, Wright PE (March 2005). "Intrinsically unstructured proteins and their functions".
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or matrix calculations, based on different structural and/or biophysical properties.
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Costantini S, Sharma A, Raucci R, Costantini M, Autiero I, Colonna G (March 2013).
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Best RB, Zhu X, Shim J, Lopes PE, Mittal J, Feig M, Mackerell AD (September 2012).
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2986:"TOP-IDP-scale: a new amino acid scale measuring propensity for intrinsic disorder"
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1700:"Young Genes are Highly Disordered as Predicted by the Preadaptation Hypothesis of
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394:
354:
different affinity values for the same system in a different concentration regime.
237:
177:
100:
92:
91:
proteins. They are sometimes considered as a separate class of proteins along with
3574:
4072:
4035:
2823:
2729:
2681:
2592:
2356:
2160:
Fuxreiter M (January 2012). "Fuzziness: linking regulation to protein dynamics".
1250:
1229:
Anfinsen CB (July 1973). "Principles that govern the folding of protein chains".
687:
326:
189:
115:
114:
interactions that are highly cooperative and dynamic, lending them importance in
96:
4050:
2304:
1776:
4055:
3001:
2703:
Minde DP, Radli M, Forneris F, Maurice MM, RΓΌdiger SG (2013). Buckle AM (ed.).
2208:
2128:
1919:
1579:
1526:
767:
543:
511:
334:
119:
88:
80:
68:
3529:
3480:
3355:
3081:
3046:
2667:
2533:
1954:
1344:
956:
817:
4081:
3721:
3628:
3263:
1825:
782:
678:
346:
209:
3963:
1761:"Gene Birth Contributes to Structural Disorder Encoded by Overlapping Genes"
1727:
646:
sites. There are different approaches for predicting IDP structure, such as
3982:
3923:
3866:
3823:
3772:
3729:
3693:
3636:
3592:
3547:
3498:
3441:
3406:
3363:
3328:
3271:
3224:
3181:
3124:
3089:
3054:
3019:
2970:
2962:
2935:
2878:
2842:
2783:
2748:
2689:
2646:
2611:
2552:
2464:
2406:
2364:
2322:
2273:
2216:
2181:
2146:
2089:
2032:
1997:
1962:
1927:
1892:
1843:
1794:
1745:
1676:
1641:
1588:
1544:
1490:
1438:
1392:
1352:
1304:
1215:
1166:
1117:
1068:
1013:
964:
918:
880:
728:
535:
24:
4004:
MobiDB: a comprehensive database of intrinsic protein disorder annotations
3146:
Wise-Scira O, Dunn A, Aloglu AK, Sakallioglu IT, Coskuner O (March 2013).
2433:"Structural disorder of monomeric Ξ±-synuclein persists in mammalian cells"
1258:
995:
366:
includes proteins that contain IDRs as well as fully disordered proteins.
3804:
3785:
3583:
2071:
2056:"Drawing on disorder: How viruses use histone mimicry to their advantage"
1874:
1084:"Intrinsically disordered proteins in cellular signalling and regulation"
777:
515:
452:
370:
318:
261:
193:
111:
76:
75:. IDPs range from fully unstructured to partially structured and include
36:
3216:
2456:
2255:
1049:
3420:
Fox SJ, Kannan S (September 2017). "Probing the dynamics of disorder".
3116:
2984:
Campen A, Williams RM, Brown CJ, Meng J, Uversky VN, Dunker AK (2008).
2917:
2173:
2024:
1472:
978:
Andreeva A, Howorth D, Chothia C, Kulesha E, Murzin AG (January 2014).
894:
440:
validation of IDR predictions is now possible using biotin 'painting'.
40:
3905:
3858:
3764:
3675:
3310:
3163:
3032:
2870:
2775:
1197:
1148:
580:
19:
2638:
801:
Majorek K, Kozlowski L, Jakalski M, Bujnicki JM (December 18, 2008).
682:
314:
273:
245:
1668:
1099:
910:
2500:
2487:
2340:
1558:
Collins MO, Yu L, Campuzano I, Grant SG, Choudhary JS (July 2008).
1511:"Interaction modules that impart specificity to disordered protein"
752:
503:
495:
217:
1180:
Song J, Lee MS, Carlberg I, Vener AV, Markley JL (December 2006).
3649:
1808:
James, Jennifer E; Nelson, Paul G; Masel, Joanna (4 April 2023).
1133:"Classification of intrinsically disordered regions and proteins"
757:
606:
499:
60:
3936:
3560:
2488:"Biotinylation by proximity labelling favours unfolded proteins"
800:
691:Ξ±-synuclein protein and associated disease mechanisms. Many key
340:
268:. They also allow their binding partners to induce larger scale
110:. For example, IDPs have been identified to participate in weak
3145:
1130:
762:
669:
as REMARK465, missing electron densities in X-ray structures).
610:
562:
to visualise the spatio-temporal flexibility of IDPs directly.
502:
groups exposed to solvent, so that they are readily cleaved by
213:
134:
3514:"Constructing ensembles for intrinsically disordered proteins"
2948:
1609:
4003:
3195:
Dobson CM (December 2003). "Protein folding and misfolding".
2797:
Neupane K, Solanki A, Sosova I, Belov M, Woodside MT (2014).
2670:
Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
2430:
980:"SCOP2 prototype: a new approach to protein structure mining"
977:
810:
Prediction of Protein Structures, Functions, and Interactions
772:
510:
and exhibit a small dispersion (<1 ppm) in their 1H amide
303:
3706:
3245:
2855:
2345:
The International Journal of Biochemistry & Cell Biology
486:. Unfolded proteins are also characterized by their lack of
3068:
Tompa P (June 2011). "Unstructural biology coming of age".
2566:
Minde DP, Maurice MM, RΓΌdiger SG (2012). Uversky VN (ed.).
2232:"Extreme disorder in an ultrahigh-affinity protein complex"
1940:
662:
527:
498:
spectroscopy. Unfolded proteins also have exposed backbone
163:
choose one when binding to other substrates. In the 1960s,
4060:
942:
2796:
2702:
2229:
1975:
1271:
847:
704:
540:
531:
526:
Bulk methods to study IDP structure and dynamics include
248:
remodeling functions. Genes that have recently been born
72:
3750:
3613:
3102:
2892:
Min D, Kim K, Hyeon C, Cho YH, Shin YK, Yoon TY (2013).
2102:
2983:
1557:
1320:
4065:
4046:
Gallery of images of intrinsically disordered proteins
2514:
2485:
4051:
First IDP journal covering all topics of IDP research
1370:
1026:
696:
inhibiting them, and thus counteracting the disease.
2761:
2696:
2194:
1856:
1179:
4040:
2565:
382:, i.e. sequences with over-representation of a few
182:
Nuclear magnetic resonance spectroscopy of proteins
3376:
2053:
1857:Prakash A, Shin J, Rajan S, Yoon HS (April 2016).
1697:
2661:
1504:
1502:
1500:
4079:
3836:
3563:Journal of Biomolecular Structure & Dynamics
3292:
3139:
1807:
1698:Wilson BA, Foy SG, Neme R, Masel J (June 2017).
154:. These early structures suggested that a fixed
71:interaction partners, such as other proteins or
3999:Intrinsically disordered protein at Proteopedia
2341:"Intrinsically disordered proteins from A to Z"
1508:
1454:
1450:
1448:
1406:
1404:
1402:
1366:
1364:
1362:
494:(esp. a pronounced minimum at ~200 nm) or
3454:
2891:
2384:
1497:
843:
841:
839:
837:
812:. John Wiley & Sons, Ltd. pp. 39β62.
617:
297:
4041:DP Database of Disordered Protein Predictions
2380:
2378:
2376:
2374:
1275:Journal of Molecular Graphics & Modelling
851:Journal of Molecular Graphics & Modelling
803:"First Steps of Protein Structure Prediction"
654:create a more competent and exact predictor.
341:Disorder in the bound state (fuzzy complexes)
3511:
3422:Progress in Biophysics and Molecular Biology
2624:
2334:
2332:
1905:
1445:
1399:
1359:
1316:
1314:
212:predictions indicate that is more common in
35:were morphed. Secondary structure elements:
3792:International Journal of Molecular Sciences
3643:
2790:
2515:Minde DP, Ramakrishna M, Lilley KS (2020).
2486:Minde DP, Ramakrishna M, Lilley KS (2018).
2286:
1758:
1173:
1081:
893:
834:
3753:Journal of Chemical Theory and Computation
3710:Journal of Chemical Theory and Computation
3617:Journal of Chemical Theory and Computation
3505:
3299:Journal of Chemical Theory and Computation
2508:
2371:
2010:
1410:
938:
936:
490:, as assessed by far-UV (170-250 nm)
401:
126:, interactions, evolution and regulation.
4061:Database of experimentally validated IDPs
3972:
3962:
3913:
3813:
3803:
3683:
3607:
3582:
3537:
3488:
3419:
3318:
3171:
3009:
2925:
2832:
2822:
2738:
2728:
2601:
2591:
2542:
2532:
2499:
2329:
2312:
2263:
2159:
2136:
2079:
1882:
1833:
1784:
1735:
1623:
1578:
1534:
1480:
1334:
1311:
1286:
1205:
1156:
1107:
1058:
1048:
1003:
862:
708:MD simulation of the Glutaredoxin 1 from
2287:Feng H, Zhou BR, Bai Y (November 2018).
1385:10.1146/annurev.biophys.37.032807.125924
1228:
703:
569:
550:to monitor secondary structure of IDPs.
459:studies may also be a sign of disorder.
288:
133:
18:
3887:
3455:Terakawa T, Takada S (September 2011).
2618:
2338:
2054:Tarakhovsky A, Prinjha RK (July 2018).
1934:
933:
699:
672:
4080:
3399:10.1146/annurev-physchem-052516-050843
3194:
2559:
1654:
1088:Nature Reviews. Molecular Cell Biology
565:
443:
304:Molecular Recognition Features (MoRFs)
3518:Current Opinion in Structural Biology
3344:Current Opinion in Structural Biology
3070:Current Opinion in Structural Biology
3067:
3035:Current Opinion in Structural Biology
2399:10.1146/annurev-biochem-072711-164947
1908:Current Protein & Peptide Science
945:Current Opinion in Structural Biology
899:Nature Reviews Molecular Cell Biology
630:
600:
421:
375:
357:
87:, or flexible linkers in large multi-
3341:
2060:The Journal of Experimental Medicine
1759:Willis S, Masel J (September 2018).
1082:Wright PE, Dyson HJ (January 2015).
637:List of disorder prediction software
16:Protein without a fixed 3D structure
3379:Annual Review of Physical Chemistry
3252:The Journal of Physical Chemistry B
1567:Molecular & Cellular Proteomics
1509:Cermakova K, Hodges HC (May 2023).
1455:Kamerlin SC, Warshel A (May 2010).
534:for atomistic ensemble refinement,
480:small angle X-ray scattering (SAXS)
255:
227:
13:
3512:Fisher CK, Stultz CM (June 2011).
1421:10.1016/B978-0-12-381262-9.00005-7
643:
520:Fast parallel proteolysis (FASTpp)
455:. The lack of electron density in
160:central dogma of molecular biology
67:, typically in the absence of its
14:
4104:
3992:
3894:Intrinsically Disordered Proteins
735:MD simulations, or methods using
3434:10.1016/j.pbiomolbio.2017.05.008
1657:Journal of Molecular Recognition
530:for ensemble shape information,
279:
220:than in known structures in the
168:observed in vitro. As stated in
53:intrinsically disordered protein
3930:
3881:
3839:The Journal of Chemical Physics
3830:
3779:
3744:
3700:
3554:
3448:
3413:
3370:
3335:
3286:
3239:
3188:
3096:
3061:
3026:
2977:
2942:
2885:
2849:
2755:
2413:
2280:
2223:
2188:
2153:
2096:
2047:
2004:
1969:
1899:
1850:
1814:Molecular Biology and Evolution
1801:
1752:
1691:
1648:
1603:
1551:
1265:
1222:
242:post-translational modification
2197:Trends in Biochemical Sciences
1978:Trends in Biochemical Sciences
1708:Nature Ecology & Evolution
1515:Trends in Biochemical Sciences
1413:Protein Structure and Diseases
1124:
1075:
1020:
971:
887:
794:
594:Disorder prediction algorithms
476:analytical ultracentrifugation
429:The first direct evidence for
146:In the 1930s-1950s, the first
63:that lacks a fixed or ordered
23:Conformational flexibility in
1:
3575:10.1080/07391102.2016.1196151
2387:Annual Review of Biochemistry
1990:10.1016/S0968-0004(03)00003-3
1634:10.1016/S0022-2836(02)00969-5
1297:10.1016/s1093-3263(00)00138-8
873:10.1016/s1093-3263(00)00138-8
788:
472:size exclusion chromatography
2824:10.1371/journal.pone.0086495
2730:10.1371/journal.pone.0077257
2682:10.1016/j.bbapap.2015.01.004
2593:10.1371/journal.pone.0046147
2357:10.1016/j.biocel.2011.04.001
1943:Journal of Molecular Biology
1612:Journal of Molecular Biology
1323:Journal of Molecular Biology
1251:10.1126/science.181.4096.223
199:
7:
2990:Protein and Peptide Letters
2305:10.1021/acs.biochem.8b01075
1777:10.1534/genetics.118.301249
1373:Annual Review of Biophysics
746:
618:Predicting IDPs by sequence
508:hydrogen-deuterium exchange
298:Coupled folding and binding
156:three-dimensional structure
65:three-dimensional structure
10:
4109:
3002:10.2174/092986608785849164
2339:Uversky VN (August 2011).
2209:10.1016/j.tibs.2011.04.006
2129:10.1038/s41598-017-18742-8
1920:10.2174/138920312799277974
1580:10.1074/mcp.M700564-MCP200
1527:10.1016/j.tibs.2023.01.004
990:(Database issue): D310β4.
634:
482:, and measurements of the
129:
3530:10.1016/j.sbi.2011.04.001
3481:10.1016/j.bpj.2011.08.003
3356:10.1016/j.sbi.2017.01.006
3152:ACS Chemical Neuroscience
3082:10.1016/j.sbi.2011.03.012
3047:10.1016/j.sbi.2011.03.014
2534:10.1038/s42003-020-0758-y
1955:10.1016/j.jmb.2006.07.087
1345:10.1016/j.jmb.2004.02.002
957:10.1016/j.sbi.2008.10.002
818:10.1002/9780470741894.ch2
4017:isordered proteins with
3943:BMC Evolutionary Biology
3722:10.1021/acs.jctc.8b01042
3629:10.1021/acs.jctc.5b00047
3264:10.1021/acs.jpcb.1c07035
380:low complexity sequences
3964:10.1186/1471-2148-13-60
1728:10.1038/s41559-017-0146
808:. In Bujnicki J (ed.).
402:Experimental validation
351:conformational ensemble
266:protein domain dynamics
152:protein crystallography
2963:10.1002/cphc.200800210
2521:Communications Biology
1863:Nucleic Acids Research
1826:10.1093/molbev/msad073
984:Nucleic Acids Research
713:
589:
457:X-ray crystallographic
331:human papillomaviruses
270:conformational changes
143:
44:
4088:Proteins by structure
4066:IDP ensemble database
2898:Nature Communications
707:
681:is the cause of many
573:
289:Pre-structured motifs
234:allosteric regulation
137:
22:
3805:10.3390/ijms20030606
2859:Analytical Chemistry
2162:Molecular BioSystems
2072:10.1084/jem.20180099
700:Computer simulations
673:Disorder and disease
108:biological functions
3955:2013BMCEE..13...60C
3888:Uversky VN (2013).
3851:2021JChPh.155l5103G
3668:2015NatSR...515449G
3473:2011BpJ...101.1450T
3461:Biophysical Journal
3391:2017ARPC...68..117C
3258:(49): 13366β13375.
3217:10.1038/nature02261
3209:2003Natur.426..884D
2910:2013NatCo...4.1705M
2815:2014PLoSO...986495N
2721:2013PLoSO...877257M
2584:2012PLoSO...746147M
2457:10.1038/nature16531
2449:2016Natur.530...45T
2256:10.1038/nature25762
2248:2018Natur.555...61B
2121:2018NatSR...8..358A
1720:2017NatEE...1..146W
1243:1973Sci...181..223A
1050:10.7554/eLife.40497
996:10.1093/nar/gkt1242
566:Disorder annotation
488:secondary structure
388:secondary structure
311:Short Linear Motifs
165:Levinthal's paradox
4071:2018-03-10 at the
4034:2020-05-02 at the
3656:Scientific Reports
3248:Trypanosoma Brucei
3117:10.1002/prot.21075
2918:10.1038/ncomms2692
2174:10.1039/c1mb05234a
2109:Scientific Reports
2025:10.1002/prot.21328
1875:10.1093/nar/gkw001
1473:10.1002/prot.22654
714:
710:Trypanosoma brucei
693:tumour suppressors
679:misfolded proteins
631:Prediction methods
601:Disorder databases
590:
548:Circular Dichroism
492:circular dichroism
484:diffusion constant
464:radius of gyration
358:Structural aspects
148:protein structures
144:
45:
4093:Protein structure
3906:10.4161/idp.25496
3859:10.1063/5.0062687
3765:10.1021/ct500287c
3676:10.1038/srep15449
3311:10.1021/ct300400x
3164:10.1021/cn3002027
2871:10.1021/ac3035025
2776:10.1021/cr400297g
2299:(48): 6645β6648.
1237:(4096): 223β230.
1198:10.1021/bi062148m
1149:10.1021/cr400525m
1143:(13): 6589β6631.
683:synucleinopathies
468:hydrodynamic drag
101:membrane proteins
49:molecular biology
4100:
3987:
3986:
3976:
3966:
3934:
3928:
3927:
3917:
3885:
3879:
3878:
3834:
3828:
3827:
3817:
3807:
3783:
3777:
3776:
3759:(6): 2224β2231.
3748:
3742:
3741:
3716:(4): 2597β2607.
3704:
3698:
3697:
3687:
3647:
3641:
3640:
3623:(6): 2776β2782.
3611:
3605:
3604:
3586:
3569:(8): 1813β1823.
3558:
3552:
3551:
3541:
3509:
3503:
3502:
3492:
3467:(6): 1450β1458.
3452:
3446:
3445:
3417:
3411:
3410:
3374:
3368:
3367:
3339:
3333:
3332:
3322:
3305:(9): 3257β3273.
3290:
3284:
3283:
3243:
3237:
3236:
3203:(6968): 884β90.
3192:
3186:
3185:
3175:
3143:
3137:
3136:
3100:
3094:
3093:
3065:
3059:
3058:
3030:
3024:
3023:
3013:
2981:
2975:
2974:
2946:
2940:
2939:
2929:
2889:
2883:
2882:
2853:
2847:
2846:
2836:
2826:
2794:
2788:
2787:
2764:Chemical Reviews
2759:
2753:
2752:
2742:
2732:
2700:
2694:
2693:
2665:
2659:
2658:
2639:10.1038/nmeth740
2622:
2616:
2615:
2605:
2595:
2563:
2557:
2556:
2546:
2536:
2512:
2506:
2505:
2503:
2483:
2477:
2476:
2428:
2422:
2417:
2411:
2410:
2382:
2369:
2368:
2351:(8): 1090β1103.
2336:
2327:
2326:
2316:
2284:
2278:
2277:
2267:
2227:
2221:
2220:
2192:
2186:
2185:
2157:
2151:
2150:
2140:
2100:
2094:
2093:
2083:
2066:(7): 1777β1787.
2051:
2045:
2044:
2008:
2002:
2001:
1973:
1967:
1966:
1938:
1932:
1931:
1903:
1897:
1896:
1886:
1869:(6): 2909β2925.
1854:
1848:
1847:
1837:
1805:
1799:
1798:
1788:
1756:
1750:
1749:
1739:
1695:
1689:
1688:
1652:
1646:
1645:
1627:
1607:
1601:
1600:
1582:
1564:
1555:
1549:
1548:
1538:
1506:
1495:
1494:
1484:
1452:
1443:
1442:
1408:
1397:
1396:
1368:
1357:
1356:
1338:
1318:
1309:
1308:
1290:
1269:
1263:
1262:
1226:
1220:
1219:
1209:
1192:(51): 15633β43.
1177:
1171:
1170:
1160:
1137:Chemical Reviews
1128:
1122:
1121:
1111:
1079:
1073:
1072:
1062:
1052:
1024:
1018:
1017:
1007:
975:
969:
968:
940:
931:
930:
891:
885:
884:
866:
845:
832:
831:
807:
798:
758:DisProt database
723:replica exchange
583:
555:optical tweezers
506:, undergo rapid
453:NMR spectroscopy
395:circuit topology
376:biological roles
256:Flexible linkers
238:enzyme catalysis
228:Biological roles
222:protein database
178:electron density
170:Anfinsen's Dogma
4108:
4107:
4103:
4102:
4101:
4099:
4098:
4097:
4078:
4077:
4073:Wayback Machine
4036:Wayback Machine
4025:nnotations and
3995:
3990:
3935:
3931:
3886:
3882:
3835:
3831:
3784:
3780:
3749:
3745:
3705:
3701:
3648:
3644:
3612:
3608:
3559:
3555:
3510:
3506:
3453:
3449:
3418:
3414:
3375:
3371:
3340:
3336:
3291:
3287:
3244:
3240:
3193:
3189:
3144:
3140:
3101:
3097:
3066:
3062:
3031:
3027:
2982:
2978:
2957:(13): 1859β66.
2947:
2943:
2890:
2886:
2854:
2850:
2795:
2791:
2770:(6): 3281β317.
2760:
2756:
2701:
2697:
2666:
2662:
2623:
2619:
2564:
2560:
2513:
2509:
2484:
2480:
2443:(7588): 45β50.
2429:
2425:
2418:
2414:
2383:
2372:
2337:
2330:
2285:
2281:
2242:(7694): 61β66.
2228:
2224:
2193:
2189:
2158:
2154:
2101:
2097:
2052:
2048:
2009:
2005:
1974:
1970:
1939:
1935:
1904:
1900:
1855:
1851:
1806:
1802:
1757:
1753:
1714:(6): 0146β146.
1696:
1692:
1669:10.1002/jmr.915
1653:
1649:
1608:
1604:
1562:
1556:
1552:
1507:
1498:
1453:
1446:
1431:
1409:
1400:
1369:
1360:
1336:10.1.1.120.5605
1319:
1312:
1270:
1266:
1227:
1223:
1178:
1174:
1129:
1125:
1100:10.1038/nrm3920
1080:
1076:
1025:
1021:
976:
972:
941:
934:
911:10.1038/nrm1589
892:
888:
846:
835:
828:
805:
799:
795:
791:
763:MobiDB database
749:
702:
675:
659:neural networks
648:neural networks
639:
633:
620:
603:
575:
568:
514:as measured by
512:chemical shifts
449:
427:
404:
360:
347:fuzzy complexes
343:
300:
291:
282:
258:
230:
202:
190:alpha-synuclein
150:were solved by
132:
43:(blue arrows).
17:
12:
11:
5:
4106:
4096:
4095:
4090:
4076:
4075:
4063:
4058:
4053:
4048:
4043:
4038:
4006:
4001:
3994:
3993:External links
3991:
3989:
3988:
3929:
3880:
3845:(12): 125103.
3829:
3778:
3743:
3699:
3642:
3606:
3553:
3524:(3): 426β431.
3504:
3447:
3412:
3369:
3334:
3285:
3238:
3187:
3158:(3): 498β508.
3138:
3095:
3076:(3): 419β425.
3060:
3025:
2996:(9): 956β963.
2976:
2941:
2884:
2865:(4): 2449β56.
2848:
2789:
2754:
2715:(10): e77257.
2695:
2660:
2627:Nature Methods
2617:
2578:(10): e46147.
2558:
2507:
2501:10.1101/274761
2478:
2423:
2412:
2370:
2328:
2279:
2222:
2187:
2152:
2095:
2046:
2003:
1968:
1949:(5): 1043β59.
1933:
1898:
1849:
1800:
1771:(1): 303β313.
1751:
1690:
1647:
1625:10.1.1.132.682
1602:
1573:(7): 1331β48.
1550:
1521:(5): 477β490.
1496:
1467:(6): 1339β75.
1444:
1429:
1398:
1358:
1310:
1288:10.1.1.113.556
1264:
1221:
1172:
1123:
1074:
1019:
970:
932:
905:(3): 197β208.
886:
864:10.1.1.113.556
833:
826:
792:
790:
787:
786:
785:
780:
775:
770:
768:Molten globule
765:
760:
755:
748:
745:
737:coarse-grained
733:multicanonical
701:
698:
674:
671:
635:Main article:
632:
629:
619:
616:
602:
599:
567:
564:
544:chemical shift
448:
442:
426:
420:
403:
400:
359:
356:
342:
339:
299:
296:
290:
287:
281:
278:
272:by long-range
257:
254:
229:
226:
201:
198:
131:
128:
120:cell signaling
116:DNA regulation
81:molten globule
69:macromolecular
15:
9:
6:
4:
3:
2:
4105:
4094:
4091:
4089:
4086:
4085:
4083:
4074:
4070:
4067:
4064:
4062:
4059:
4057:
4054:
4052:
4049:
4047:
4044:
4042:
4039:
4037:
4033:
4030:
4028:
4024:
4020:
4016:
4013:ntrinsically
4012:
4007:
4005:
4002:
4000:
3997:
3996:
3984:
3980:
3975:
3970:
3965:
3960:
3956:
3952:
3948:
3944:
3940:
3933:
3925:
3921:
3916:
3911:
3907:
3903:
3900:(1): e25496.
3899:
3895:
3891:
3884:
3876:
3872:
3868:
3864:
3860:
3856:
3852:
3848:
3844:
3840:
3833:
3825:
3821:
3816:
3811:
3806:
3801:
3797:
3793:
3789:
3782:
3774:
3770:
3766:
3762:
3758:
3754:
3747:
3739:
3735:
3731:
3727:
3723:
3719:
3715:
3711:
3703:
3695:
3691:
3686:
3681:
3677:
3673:
3669:
3665:
3661:
3657:
3653:
3646:
3638:
3634:
3630:
3626:
3622:
3618:
3610:
3602:
3598:
3594:
3590:
3585:
3584:11311/1004711
3580:
3576:
3572:
3568:
3564:
3557:
3549:
3545:
3540:
3535:
3531:
3527:
3523:
3519:
3515:
3508:
3500:
3496:
3491:
3486:
3482:
3478:
3474:
3470:
3466:
3462:
3458:
3451:
3443:
3439:
3435:
3431:
3427:
3423:
3416:
3408:
3404:
3400:
3396:
3392:
3388:
3384:
3380:
3373:
3365:
3361:
3357:
3353:
3349:
3345:
3338:
3330:
3326:
3321:
3316:
3312:
3308:
3304:
3300:
3296:
3289:
3281:
3277:
3273:
3269:
3265:
3261:
3257:
3253:
3249:
3242:
3234:
3230:
3226:
3222:
3218:
3214:
3210:
3206:
3202:
3198:
3191:
3183:
3179:
3174:
3169:
3165:
3161:
3157:
3153:
3149:
3142:
3134:
3130:
3126:
3122:
3118:
3114:
3110:
3106:
3099:
3091:
3087:
3083:
3079:
3075:
3071:
3064:
3056:
3052:
3048:
3044:
3040:
3036:
3029:
3021:
3017:
3012:
3007:
3003:
2999:
2995:
2991:
2987:
2980:
2972:
2968:
2964:
2960:
2956:
2952:
2945:
2937:
2933:
2928:
2923:
2919:
2915:
2911:
2907:
2903:
2899:
2895:
2888:
2880:
2876:
2872:
2868:
2864:
2860:
2852:
2844:
2840:
2835:
2830:
2825:
2820:
2816:
2812:
2809:(1): e86495.
2808:
2804:
2800:
2793:
2785:
2781:
2777:
2773:
2769:
2765:
2758:
2750:
2746:
2741:
2736:
2731:
2726:
2722:
2718:
2714:
2710:
2706:
2699:
2691:
2687:
2683:
2679:
2676:(5): 381β90.
2675:
2671:
2664:
2656:
2652:
2648:
2644:
2640:
2636:
2633:(3): 207β12.
2632:
2628:
2621:
2613:
2609:
2604:
2599:
2594:
2589:
2585:
2581:
2577:
2573:
2569:
2562:
2554:
2550:
2545:
2540:
2535:
2530:
2526:
2522:
2518:
2511:
2502:
2497:
2493:
2489:
2482:
2474:
2470:
2466:
2462:
2458:
2454:
2450:
2446:
2442:
2438:
2434:
2427:
2421:
2416:
2408:
2404:
2400:
2396:
2392:
2388:
2381:
2379:
2377:
2375:
2366:
2362:
2358:
2354:
2350:
2346:
2342:
2335:
2333:
2324:
2320:
2315:
2310:
2306:
2302:
2298:
2294:
2290:
2283:
2275:
2271:
2266:
2261:
2257:
2253:
2249:
2245:
2241:
2237:
2233:
2226:
2218:
2214:
2210:
2206:
2203:(8): 415β23.
2202:
2198:
2191:
2183:
2179:
2175:
2171:
2168:(1): 168β77.
2167:
2163:
2156:
2148:
2144:
2139:
2134:
2130:
2126:
2122:
2118:
2114:
2110:
2106:
2099:
2091:
2087:
2082:
2077:
2073:
2069:
2065:
2061:
2057:
2050:
2042:
2038:
2034:
2030:
2026:
2022:
2019:(1): 109β22.
2018:
2014:
2007:
1999:
1995:
1991:
1987:
1983:
1979:
1972:
1964:
1960:
1956:
1952:
1948:
1944:
1937:
1929:
1925:
1921:
1917:
1913:
1909:
1902:
1894:
1890:
1885:
1880:
1876:
1872:
1868:
1864:
1860:
1853:
1845:
1841:
1836:
1831:
1827:
1823:
1819:
1815:
1811:
1804:
1796:
1792:
1787:
1782:
1778:
1774:
1770:
1766:
1762:
1755:
1747:
1743:
1738:
1733:
1729:
1725:
1721:
1717:
1713:
1709:
1705:
1703:
1694:
1686:
1682:
1678:
1674:
1670:
1666:
1662:
1658:
1651:
1643:
1639:
1635:
1631:
1626:
1621:
1618:(3): 573β84.
1617:
1613:
1606:
1598:
1594:
1590:
1586:
1581:
1576:
1572:
1568:
1561:
1554:
1546:
1542:
1537:
1532:
1528:
1524:
1520:
1516:
1512:
1505:
1503:
1501:
1492:
1488:
1483:
1478:
1474:
1470:
1466:
1462:
1458:
1451:
1449:
1440:
1436:
1432:
1430:9780123812629
1426:
1422:
1418:
1414:
1407:
1405:
1403:
1394:
1390:
1386:
1382:
1378:
1374:
1367:
1365:
1363:
1354:
1350:
1346:
1342:
1337:
1332:
1329:(3): 635β45.
1328:
1324:
1317:
1315:
1306:
1302:
1298:
1294:
1289:
1284:
1280:
1276:
1268:
1260:
1256:
1252:
1248:
1244:
1240:
1236:
1232:
1225:
1217:
1213:
1208:
1203:
1199:
1195:
1191:
1187:
1183:
1176:
1168:
1164:
1159:
1154:
1150:
1146:
1142:
1138:
1134:
1127:
1119:
1115:
1110:
1105:
1101:
1097:
1093:
1089:
1085:
1078:
1070:
1066:
1061:
1056:
1051:
1046:
1042:
1038:
1034:
1032:
1023:
1015:
1011:
1006:
1001:
997:
993:
989:
985:
981:
974:
966:
962:
958:
954:
951:(6): 756β64.
950:
946:
939:
937:
928:
924:
920:
916:
912:
908:
904:
900:
896:
890:
882:
878:
874:
870:
865:
860:
856:
852:
844:
842:
840:
838:
829:
827:9780470517673
823:
819:
815:
811:
804:
797:
793:
784:
783:Dark proteome
781:
779:
776:
774:
771:
769:
766:
764:
761:
759:
756:
754:
751:
750:
744:
740:
738:
734:
730:
726:
725:simulations,
724:
718:
711:
706:
697:
694:
689:
684:
680:
670:
668:
664:
660:
655:
651:
649:
645:
638:
628:
624:
615:
612:
608:
598:
595:
587:
582:
578:
572:
563:
561:
556:
551:
549:
545:
542:
537:
533:
529:
524:
521:
517:
513:
509:
505:
501:
497:
493:
489:
485:
481:
477:
473:
469:
465:
460:
458:
454:
446:
441:
439:
436:Larger-scale
434:
432:
424:
419:
417:
413:
409:
399:
396:
391:
389:
385:
381:
377:
372:
367:
363:
355:
352:
348:
338:
336:
332:
328:
324:
320:
316:
312:
307:
305:
295:
286:
280:Linear motifs
277:
275:
271:
267:
263:
253:
251:
247:
243:
239:
235:
225:
223:
219:
215:
211:
210:bioinformatic
206:
197:
195:
191:
185:
183:
179:
174:
171:
166:
161:
157:
153:
149:
141:
136:
127:
125:
121:
117:
113:
109:
104:
102:
98:
94:
90:
86:
82:
78:
74:
70:
66:
62:
58:
54:
50:
42:
38:
34:
30:
27:protein (PDB:
26:
21:
4026:
4022:
4018:
4014:
4010:
3946:
3942:
3932:
3897:
3893:
3883:
3842:
3838:
3832:
3795:
3791:
3781:
3756:
3752:
3746:
3713:
3709:
3702:
3659:
3655:
3645:
3620:
3616:
3609:
3566:
3562:
3556:
3521:
3517:
3507:
3464:
3460:
3450:
3425:
3421:
3415:
3382:
3378:
3372:
3347:
3343:
3337:
3302:
3298:
3288:
3255:
3251:
3247:
3241:
3200:
3196:
3190:
3155:
3151:
3141:
3108:
3104:
3098:
3073:
3069:
3063:
3041:(3): 412β8.
3038:
3034:
3028:
2993:
2989:
2979:
2954:
2951:ChemPhysChem
2950:
2944:
2901:
2897:
2887:
2862:
2858:
2851:
2806:
2802:
2792:
2767:
2763:
2757:
2712:
2708:
2698:
2673:
2669:
2663:
2630:
2626:
2620:
2575:
2571:
2561:
2524:
2520:
2510:
2491:
2481:
2440:
2436:
2426:
2415:
2390:
2386:
2348:
2344:
2296:
2293:Biochemistry
2292:
2282:
2239:
2235:
2225:
2200:
2196:
2190:
2165:
2161:
2155:
2112:
2108:
2098:
2063:
2059:
2049:
2016:
2012:
2006:
1981:
1977:
1971:
1946:
1942:
1936:
1914:(1): 34β54.
1911:
1907:
1901:
1866:
1862:
1852:
1817:
1813:
1803:
1768:
1764:
1754:
1711:
1707:
1701:
1693:
1660:
1656:
1650:
1615:
1611:
1605:
1570:
1566:
1553:
1518:
1514:
1464:
1460:
1412:
1376:
1372:
1326:
1322:
1281:(1): 26β59.
1278:
1274:
1267:
1234:
1230:
1224:
1189:
1186:Biochemistry
1185:
1175:
1140:
1136:
1126:
1094:(1): 18β29.
1091:
1087:
1077:
1040:
1036:
1030:
1022:
987:
983:
973:
948:
944:
902:
898:
889:
857:(1): 26β59.
854:
850:
809:
796:
741:
729:metadynamics
727:
719:
715:
709:
676:
656:
652:
644:linear motif
640:
625:
621:
604:
591:
552:
536:Fluorescence
525:
461:
450:
444:
437:
435:
430:
428:
422:
415:
411:
407:
405:
392:
368:
364:
361:
344:
319:Hendra virus
308:
301:
292:
283:
259:
231:
207:
203:
186:
175:
145:
105:
56:
52:
46:
4056:IDP Journal
3385:: 117β134.
3350:: 147β154.
3111:(1): 1β14.
2904:(4): 1705.
2393:: 553β584.
1984:(2): 81β5.
1704:Gene Birth"
778:Random coil
688:Ξ±-synuclein
371:hydrophobic
315:RNA viruses
262:amino acids
112:multivalent
77:random coil
4082:Categories
3798:(3): 606.
2115:(1): 358.
1663:(1): 1β8.
1379:: 215β46.
1043:: e40497.
1031:Drosophila
789:References
470:, such as
447:approaches
425:approaches
337:proteins.
85:aggregates
33:NMR models
4029:iterature
4021:xtensive
3949:(1): 60.
3875:238249229
3662:: 15449.
3601:205576649
3428:: 57β62.
3280:244942842
2527:(1): 38.
1620:CiteSeerX
1331:CiteSeerX
1283:CiteSeerX
859:CiteSeerX
667:PDB files
504:proteases
335:host cell
274:allostery
246:chromatin
218:proteomes
200:Abundance
41:Ξ²-strands
37:Ξ±-helices
4069:Archived
4032:Archived
4009:IDEAL -
3983:23497088
3924:28516015
3867:34598583
3824:30708941
3773:26580746
3738:75138292
3730:30855964
3694:26498066
3637:26575570
3593:27366858
3548:21530234
3499:21943426
3442:28554553
3407:28226222
3364:28259050
3329:23341755
3272:34870419
3225:14685248
3182:23374074
3133:30231497
3125:16856179
3105:Proteins
3090:21514142
3055:21514145
3020:18991772
2971:18698566
2936:23591872
2879:23327569
2843:24475132
2803:PLOS ONE
2784:24432838
2749:24130866
2709:PLOS ONE
2690:25603119
2655:21364478
2647:15782190
2612:23056252
2572:PLOS ONE
2553:31969649
2465:26808899
2407:24606139
2365:21501695
2323:30430826
2274:29466338
2217:21620710
2182:21927770
2147:29321677
2090:29934321
2041:96719019
2033:17407165
2013:Proteins
1998:12575995
1963:16935303
1928:22044148
1893:26762975
1844:36947137
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