The Experts below are selected from a list of 9396 Experts worldwide ranked by ideXlab platform
V.n. Uversky - One of the best experts on this subject based on the ideXlab platform.
-
Intrinsically Disordered Proteins and their `mysterious' (meta)physics
Frontiers in Physics, 2019Co-Authors: V.n. UverskyAbstract:Recognition of the natural abundance and functional importance of Intrinsically Disordered Proteins (IDPs) and hybrid Proteins containing ordered and Intrinsically Disordered protein regions (IDPRs) is changing protein science. IDPs and IDPRs; i.e., functional Proteins and protein regions without unique structures, are commonly found in all organisms, where they have crucial roles in various biological processes. Disorder-based functionality complements functions of ordered Proteins and domains. However, by virtue of their existence, IDPs/IDPRs, which are characterized by the remarkable conformational flexibility and structural plasticity, break multiple rules elaborated over the years to explain structure, folding, and functionality of well-folded Proteins with unique structures. Despite the general believe, which dominated in protein science for more than a century, that unique biological functions of Proteins require unique 3D-structures, structure-less IDPs/IDPRs are functional, being able to perform impossible tricks and to be engaged in biological activities, which are improbable for ordered Proteins. With their exceptional spatio-temporal heterogeneity and high conformational flexibility, IDPs/IDPRs represent complex systems that act at the edge of chaos and are specifically tunable by various means. In this article, some of the wanders of intrinsic disorder are discussed as illustrations of their ‘mysterious’ (meta)physics.
-
Introduction to Intrinsically Disordered Proteins and regions
Intrinsically Disordered Proteins, 2019Co-Authors: Christopher J. Oldfield, V.n. Uversky, A.k. Dunker, Lukasz KurganAbstract:Abstract Intrinsically Disordered Proteins (IDPs) and Intrinsically Disordered regions (IDRs) are fascinating dynamic conformational ensembles that are observed under physiological conditions. They facilitate a wide variety of biological processes via mechanisms that are distinct from their structured counterparts. Intrinsic disorder enables complex regulation using concerted molecular recognition, posttranslational modification, and alternative splicing. A broad analysis of IDRs reveals their central role in molecular recognition and cellular regulation. The diverse functions of IDRs are complemented by their diverse biophysical properties. Under the single moniker of disorder exist a variety of protein states that vary from protein-to-protein or for the same protein in different biological contexts. The biophysical and functional properties of IDRs are reflected in their composition, sequence complexity, and conservation. These sequence properties have been leveraged to design algorithms that accurately predict intrinsic disorder and certain molecular functions of disorder directly from the protein sequence.
-
Intrinsically Disordered Proteins in the nucleus of human cells
Biochemistry and biophysics reports, 2015Co-Authors: Telma Frege, V.n. UverskyAbstract:Abstract Intrinsically Disordered Proteins are known to perform a variety of important functions such as macromolecular recognition, promiscuous binding, and signaling. They are crucial players in various cellular pathway and processes, where they often have key regulatory roles. Among vital cellular processes intimately linked to the Intrinsically Disordered Proteins is transcription, an intricate biological performance predominantly developing inside the cell nucleus. With this work, we gathered information about Proteins that exist in various compartments and sub-nuclear bodies of the nucleus of the human cells, with the goal of identifying which ones are highly Disordered and which functions are ascribed to the Disordered nuclear Proteins.
-
Intrinsically Disordered Proteins and novel strategies for drug discovery
Expert Opinion on Drug Discovery, 2012Co-Authors: V.n. UverskyAbstract:Introduction: There is a natural abundance of Intrinsically Disordered Proteins or Intrinsically Disordered protein regions (IDPs or IDPRs), that is, biologically active Proteins/regions without stable structure. Their wide functional repertoire; the ability to participate in multiple interactions; the capability to fold at binding in a template-dependent manner and their common involvement in the pathogenesis of numerous human diseases suggest that these Proteins should be seriously considered as novel drug targets. Areas covered: This article describes the major classes of ordered Proteins traditionally used as drug targets and introduces the molecular mechanisms of drugs targeting ordered Proteins. Furthermore, it illustrates basic ways of rational drug design for these Proteins, and shows why these approaches cannot be directly used for intrinsic disorder-based drug design. Some of the new approaches utilized for finding drugs targeting IDPs/IDPRs are introduced. Expert opinion: There is a continuing ...
-
3.9 Intrinsically Disordered Proteins
Comprehensive Biophysics, 2012Co-Authors: V.n. Uversky, A.k. DunkerAbstract:This chapter introduces Intrinsically Disordered Proteins, which do not have rigid three-dimensional (3-D) structures under physiological conditions, but which nevertheless carry out numerous biological functions. Such Proteins challenge the prevailing structure-function paradigm, according to which the unique 3-D structure of a protein is a prerequisite to its function. Here we argue that the prevailing paradigm needs to be expanded to include Intrinsically Disordered Proteins and their new relationships among protein sequence, structure, and function. Since this extended paradigm opens new levels of understanding of the complex life of Proteins, it represents a major breakthrough for biochemistry, biophysics, and molecular biology.
Collin M. Stultz - One of the best experts on this subject based on the ideXlab platform.
-
constructing ensembles for Intrinsically Disordered Proteins
Current Opinion in Structural Biology, 2011Co-Authors: Charles K. Fisher, Collin M. StultzAbstract:The relatively flat energy landscapes associated with Intrinsically Disordered Proteins makes modeling these systems especially problematic. A comprehensive model for these Proteins requires one to build an ensemble consisting of a finite collection of structures, and their corresponding relative stabilities, which adequately capture the range of accessible states of the protein. In this regard, methods that use computational techniques to interpret experimental data in terms of such ensembles are an essential part of the modeling process. In this review, we critically assess the advantages and limitations of current techniques and discuss new methods for the validation of these ensembles.
-
Constructing ensembles for Intrinsically Disordered Proteins
Current Opinion in Structural Biology, 2011Co-Authors: Charles K. Fisher, Collin M. StultzAbstract:The relatively flat energy landscapes associated with Intrinsically Disordered Proteins makes modeling these systems especially problematic. A comprehensive model for these Proteins requires one to build an ensemble consisting of a finite collection of structures, and their corresponding relative stabilities, which adequately capture the range of accessible states of the protein. In this regard, methods that use computational techniques to interpret experimental data in terms of such ensembles are an essential part of the modeling process. In this review, we critically assess the advantages and limitations of current techniques and discuss new methods for the validation of these ensembles. © 2011 Elsevier Ltd.
Benjamin Schuler - One of the best experts on this subject based on the ideXlab platform.
-
perspective chain dynamics of unfolded and Intrinsically Disordered Proteins from nanosecond fluorescence correlation spectroscopy combined with single molecule fret
Journal of Chemical Physics, 2018Co-Authors: Benjamin SchulerAbstract:The dynamics of unfolded Proteins are important both for the process of protein folding and for the behavior of Intrinsically Disordered Proteins. However, methods for investigating the global chain dynamics of these structurally diverse systems have been limited. A versatile experimental approach is single-molecule spectroscopy in combination with Forster resonance energy transfer and nanosecond fluorescence correlation spectroscopy. The concepts of polymer physics offer a powerful framework both for interpreting the results and for understanding and classifying the properties of unfolded and Intrinsically Disordered Proteins. This information on long-range chain dynamics can be complemented with spectroscopic techniques that probe different length scales and time scales, and integration of these results greatly benefits from recent advances in molecular simulations. This increasing convergence between the experiment, theory, and simulation is thus starting to enable an increasingly detailed view of the dynamics of Disordered Proteins.The dynamics of unfolded Proteins are important both for the process of protein folding and for the behavior of Intrinsically Disordered Proteins. However, methods for investigating the global chain dynamics of these structurally diverse systems have been limited. A versatile experimental approach is single-molecule spectroscopy in combination with Forster resonance energy transfer and nanosecond fluorescence correlation spectroscopy. The concepts of polymer physics offer a powerful framework both for interpreting the results and for understanding and classifying the properties of unfolded and Intrinsically Disordered Proteins. This information on long-range chain dynamics can be complemented with spectroscopic techniques that probe different length scales and time scales, and integration of these results greatly benefits from recent advances in molecular simulations. This increasing convergence between the experiment, theory, and simulation is thus starting to enable an increasingly detailed view of the ...
-
quantifying internal friction in unfolded and Intrinsically Disordered Proteins with single molecule spectroscopy
Proceedings of the National Academy of Sciences of the United States of America, 2012Co-Authors: Andrea Soranno, Sonja Mullerspath, Daniel Nettels, Brigitte Buchli, Ryan R Cheng, Shawn H Pfeil, Armin Hoffmann, Everett A Lipman, Dmitrii E Makarov, Benjamin SchulerAbstract:Internal friction, which reflects the “roughness” of the energy landscape, plays an important role for Proteins by modulating the dynamics of their folding and other conformational changes. However, the experimental quantification of internal friction and its contribution to folding dynamics has remained challenging. Here we use the combination of single-molecule Forster resonance energy transfer, nanosecond fluorescence correlation spectroscopy, and microfluidic mixing to determine the reconfiguration times of unfolded Proteins and investigate the mechanisms of internal friction contributing to their dynamics. Using concepts from polymer dynamics, we determine internal friction with three complementary, largely independent, and consistent approaches as an additive contribution to the reconfiguration time of the unfolded state. We find that the magnitude of internal friction correlates with the compactness of the unfolded protein: its contribution dominates the reconfiguration time of approximately 100 ns of the compact unfolded state of a small cold shock protein under native conditions, but decreases for more expanded chains, and approaches zero both at high denaturant concentrations and in Intrinsically Disordered Proteins that are expanded due to intramolecular charge repulsion. Our results suggest that internal friction in the unfolded state will be particularly relevant for the kinetics of Proteins that fold in the microsecond range or faster. The low internal friction in expanded Intrinsically Disordered Proteins may have implications for the dynamics of their interactions with cellular binding partners.
-
polymer scaling laws of unfolded and Intrinsically Disordered Proteins quantified with single molecule spectroscopy
Proceedings of the National Academy of Sciences of the United States of America, 2012Co-Authors: Hagen Hofmann, Andrea Soranno, Daniel Nettels, Alessandro Borgia, Klaus Gast, Benjamin SchulerAbstract:The dimensions of unfolded and Intrinsically Disordered Proteins are highly dependent on their amino acid composition and solution conditions, especially salt and denaturant concentration. However, the quantitative implications of this behavior have remained unclear, largely because the effective theta-state, the central reference point for the underlying polymer collapse transition, has eluded experimental determination. Here, we used single-molecule fluorescence spectroscopy and two-focus correlation spectroscopy to determine the theta points for six different Proteins. While the scaling exponents of all Proteins converge to 0.62 ± 0.03 at high denaturant concentrations, as expected for a polymer in good solvent, the scaling regime in water strongly depends on sequence composition. The resulting average scaling exponent of 0.46 ± 0.05 for the four foldable protein sequences in our study suggests that the aqueous cellular milieu is close to effective theta conditions for unfolded Proteins. In contrast, two Intrinsically Disordered Proteins do not reach the Θ-point under any of our solvent conditions, which may reflect the optimization of their expanded state for the interactions with cellular partners. Sequence analyses based on our results imply that foldable sequences with more compact unfolded states are a more recent result of protein evolution.
-
charge interactions can dominate the dimensions of Intrinsically Disordered Proteins
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Sonja Mullerspath, Andrea Soranno, Verena Hirschfeld, Hagen Hofmann, Stefan Ruegger, Luc Reymond, Daniel Nettels, Benjamin SchulerAbstract:Many eukaryotic Proteins are Disordered under physiological conditions, and fold into ordered structures only on binding to their cellular targets. Such Intrinsically Disordered Proteins (IDPs) often contain a large fraction of charged amino acids. Here, we use single-molecule Forster resonance energy transfer to investigate the influence of charged residues on the dimensions of unfolded and Intrinsically Disordered Proteins. We find that, in contrast to the compact unfolded conformations that have been observed for many Proteins at low denaturant concentration, IDPs can exhibit a prominent expansion at low ionic strength that correlates with their net charge. Charge-balanced polypeptides, however, can exhibit an additional collapse at low ionic strength, as predicted by polyampholyte theory from the attraction between opposite charges in the chain. The pronounced effect of charges on the dimensions of unfolded Proteins has important implications for the cellular functions of IDPs.
-
from the cover charge interactions can dominate the dimensions of Intrinsically Disordered Proteins
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Sonja Mullerspath, Andrea Soranno, Verena Hirschfeld, Hagen Hofmann, Stefan Ruegger, Luc Reymond, Daniel Nettels, Benjamin SchulerAbstract:Many eukaryotic Proteins are Disordered under physiological conditions, and fold into ordered structures only on binding to their cellular targets. Such Intrinsically Disordered Proteins (IDPs) often contain a large fraction of charged amino acids. Here, we use single-molecule Forster resonance energy transfer to investigate the influence of charged residues on the dimensions of unfolded and Intrinsically Disordered Proteins. We find that, in contrast to the compact unfolded conformations that have been observed for many Proteins at low denaturant concentration, IDPs can exhibit a prominent expansion at low ionic strength that correlates with their net charge. Charge-balanced polypeptides, however, can exhibit an additional collapse at low ionic strength, as predicted by polyampholyte theory from the attraction between opposite charges in the chain. The pronounced effect of charges on the dimensions of unfolded Proteins has important implications for the cellular functions of IDPs.
Martin Blackledge - One of the best experts on this subject based on the ideXlab platform.
-
an Intrinsically Disordered Proteins community for elixir
F1000Research, 2019Co-Authors: Norman E Davey, Martin Blackledge, Madan M Babu, Alan Bridge, Salvador Capellagutierrez, Zsuzsanna Dosztanyi, Rachel Drysdale, Richard J Edwards, Arne Elofsson, Isabella C. FelliAbstract:Intrinsically Disordered Proteins (IDPs) and Intrinsically Disordered regions (IDRs) are now recognised as major determinants in cellular regulation. This white paper presents a roadmap for future e-infrastructure developments in the field of IDP research within the ELIXIR framework. The goal of these developments is to drive the creation of high-quality tools and resources to support the identification, analysis and functional characterisation of IDPs. The roadmap is the result of a workshop titled “An Intrinsically Disordered protein user community proposal for ELIXIR” held at the University of Padua. The workshop, and further consultation with the members of the wider IDP community, identified the key priority areas for the roadmap including the development of standards for data annotation, storage and dissemination; integration of IDP data into the ELIXIR Core Data Resources; and the creation of benchmarking criteria for IDP-related software. Here, we discuss these areas of priority, how they can be implemented in cooperation with the ELIXIR platforms, and their connections to existing ELIXIR Communities and international consortia. The article provides a preliminary blueprint for an IDP Community in ELIXIR and is an appeal to identify and involve new stakeholders.
-
solvent dependent segmental dynamics in Intrinsically Disordered Proteins
Science Advances, 2019Co-Authors: Nicola Salvi, Anton Abyzov, Martin BlackledgeAbstract:Protein and water dynamics have a synergistic relationship, which is particularly important for Intrinsically Disordered Proteins (IDPs), although the details of this coupling remain poorly understood. Here, we combine temperature-dependent molecular dynamics simulations using different water models with extensive nuclear magnetic resonance (NMR) relaxation to examine the importance of distinct modes of solvent and solute motion for the accurate reproduction of site-specific dynamics in IDPs. We find that water dynamics play a key role in motional processes internal to “segments” of IDPs, stretches of primary sequence that share dynamic properties and behave as discrete dynamic units. We identify a relationship between the time scales of intrasegment dynamics and the lifetime of hydrogen bonds in bulk water. Correct description of these motions is essential for accurate reproduction of protein relaxation. Our findings open important perspectives for understanding the role of hydration water on the behavior and function of IDPs in solution.
-
long range correlated dynamics in Intrinsically Disordered Proteins
Journal of the American Chemical Society, 2014Co-Authors: Giacomo Parigi, Markus Zweckstetter, Stefan Becker, Martin Blackledge, Nasrollah Rezaeighaleh, Andrea Giachetti, Claudio O Fernandez, Christian Griesinger, Claudio LuchinatAbstract:Intrinsically Disordered Proteins (IDPs) are involved in a wide variety of physiological and pathological processes and are best described by ensembles of rapidly interconverting conformers. Using fast field cycling relaxation measurements we here show that the IDP α-synuclein as well as a variety of other IDPs undergoes slow reorientations at time scales comparable to folded Proteins. The slow motions are not perturbed by mutations in α-synuclein, which are related to genetic forms of Parkinson’s disease, and do not depend on secondary and tertiary structural propensities. Ensemble-based hydrodynamic calculations suggest that the time scale of the underlying correlated motion is largely determined by hydrodynamic coupling between locally rigid segments. Our study indicates that long-range correlated dynamics are an intrinsic property of IDPs and offers a general physical mechanism of correlated motions in highly flexible biomolecular systems.
-
testing the validity of ensemble descriptions of Intrinsically Disordered Proteins
Proceedings of the National Academy of Sciences of the United States of America, 2014Co-Authors: Malene Ringkjøbing Jensen, Martin BlackledgeAbstract:Understanding biological function in the profusion of Proteins containing significant levels of intrinsic disorder depends on how accurately we can describe their conformational behavior (1). Recently, Wang et al. used molecular dynamics (MD) techniques to study the molecular recognition element of the C-terminal domain of the measles virus nucleoprotein (MeV-NTAIL), an example of this enigmatic family of Intrinsically Disordered Proteins (IDPs) (2). In justifying their approach, the authors state that “in general, it is not feasible to characterize IDPs by an ensemble averaged method due to the underlying structural heterogeneity.” Although the potential advantages of restraint-free MD in terms of dynamic time scales are evident, numerous developments in the field also exploit ensemble-averaged NMR data to derive molecular descriptions of IDPs.
-
Intrinsically Disordered Proteins implicated in paramyxoviral replication machinery.
Current Opinion in Virology, 2014Co-Authors: Guillaume Communie, Rob W. H. Ruigrok, Malene Ringkjøbing Jensen, Martin BlackledgeAbstract:The development of mechanistic insight into the molecular basis of how Intrinsically Disordered Proteins function is a key challenge for contemporary molecular biology. Intrinsic protein disorder is abundant in the replication machinery of paramyxoviruses. In order to study this kind of protein, new methods are required that specifically take account of the highly dynamic nature of the chain, and describe this disorder in quantitative terms. Here we review recent studies of conformational disorder in paramyxoviral phosphoProteins and nucleoProteins using solution-based approaches such as nuclear magnetic resonance.
Christopher J. Oldfield - One of the best experts on this subject based on the ideXlab platform.
-
Introduction to Intrinsically Disordered Proteins and regions
Intrinsically Disordered Proteins, 2019Co-Authors: Christopher J. Oldfield, V.n. Uversky, A.k. Dunker, Lukasz KurganAbstract:Abstract Intrinsically Disordered Proteins (IDPs) and Intrinsically Disordered regions (IDRs) are fascinating dynamic conformational ensembles that are observed under physiological conditions. They facilitate a wide variety of biological processes via mechanisms that are distinct from their structured counterparts. Intrinsic disorder enables complex regulation using concerted molecular recognition, posttranslational modification, and alternative splicing. A broad analysis of IDRs reveals their central role in molecular recognition and cellular regulation. The diverse functions of IDRs are complemented by their diverse biophysical properties. Under the single moniker of disorder exist a variety of protein states that vary from protein-to-protein or for the same protein in different biological contexts. The biophysical and functional properties of IDRs are reflected in their composition, sequence complexity, and conservation. These sequence properties have been leveraged to design algorithms that accurately predict intrinsic disorder and certain molecular functions of disorder directly from the protein sequence.
-
Intrinsically Disordered Proteins and multicellular organisms
Seminars in Cell & Developmental Biology, 2015Co-Authors: Keith A Dunker, Sarah E Bondos, Fei Huang, Christopher J. OldfieldAbstract:Abstract Intrinsically Disordered Proteins (IDPs) and IDP regions lack stable tertiary structure yet carry out numerous biological functions, especially those associated with signaling, transcription regulation, DNA condensation, cell division, and cellular differentiation. Both post-translational modifications (PTMs) and alternative splicing (AS) expand the functional repertoire of IDPs. Here we propose that an “IDP-based developmental toolkit,” which is comprised of IDP regions, PTMs, especially multiple PTMs, within these IDP regions, and AS events within segments of pre-mRNA that code for these same IDP regions, allows functional diversification and environmental responsiveness for molecules that direct the development of complex metazoans.
-
Intrinsically Disordered Proteins and Intrinsically Disordered protein regions
Annual Review of Biochemistry, 2014Co-Authors: Christopher J. Oldfield, Keith A DunkerAbstract:Intrinsically Disordered Proteins (IDPs) and IDP regions fail to form a stable structure, yet they exhibit biological activities. Their mobile flexibility and structural instability are encoded by their amino acid sequences. They recognize Proteins, nucleic acids, and other types of partners; they accelerate interactions and chemical reactions between bound partners; and they help accommodate posttranslational modifications, alternative splicing, protein fusions, and insertions or deletions. Overall, IDP-associated biological activities complement those of structured Proteins. Recently, there has been an explosion of studies on IDP regions and their functions, yet the discovery and investigation of these Proteins have a long, mostly ignored history. Along with recent discoveries, we present several early examples and the mechanisms by which IDPs contribute to function, which we hope will encourage comprehensive discussion of IDPs and IDP regions in biochemistry textbooks. Finally, we propose future direct...
-
archaic chaos Intrinsically Disordered Proteins in archaea
BMC Systems Biology, 2010Co-Authors: Robert W Williams, V.n. Uversky, Christopher J. Oldfield, Keith A DunkerAbstract:Background Many Proteins or their regions known as Intrinsically Disordered Proteins (IDPs) and Intrinsically Disordered regions (IDRs) lack unique 3D structure in their native states under physiological conditions yet fulfill key biological functions. Earlier bioinformatics studies showed that IDPs and IDRs are highly abundant in different proteomes and carry out mostly regulatory functions related to molecular recognition and signal transduction. Archaea belong to an intriguing domain of life whose members, being microbes, are characterized by a unique mosaic-like combination of bacterial and eukaryotic properties and include inhabitants of some of the most extreme environments on the planet. With the expansion of the archaea genome data (more than fifty archaea species from five different phyla are known now), and with recent improvements in the accuracy of intrinsic disorder prediction, it is time to re-examine the abundance of IDPs and IDRs in the archaea domain.
-
IEEE 7 th BIBE Invited Tutorial Lecture: Intrinsically Disordered Proteins in Human Diseases
2007 IEEE 7th International Symposium on BioInformatics and BioEngineering, 2007Co-Authors: V.n. Uversky, Christopher J. Oldfield, A.k. DunkerAbstract:Intrinsically Disordered Proteins lack stable tertiary and/or secondary structure under physiological conditions in vitro. They are highly abundant in nature, with ~25-30% of eukaryotic Proteins being mostly Disordered, and with >50% of eukaryotic Proteins and > 70% of signaling Proteins having long Disordered regions. Functional repertoire of Intrinsically Disordered Proteins is very broad and complements functions of ordered Proteins. Often, Intrinsically Disordered Proteins are involved in regulation, signaling and control pathways, where binding to multiple partners and high-speciflcity/low-afflnity interactions play a crucial role. We have found that out of the 711 Swiss-Prot functional keywords associated with at least 20 Proteins, 262 were strongly positively correlated with long Intrinsically Disordered regions, and 302 were strongly negatively correlated. It is suggested that functions of Intrinsically Disordered Proteins may arise from the specific disorder form, from inter-conversion of Disordered forms, or from transitions between Disordered and ordered conformations. The choice between these conformations is determined by the peculiarities of the protein environment, and many Intrinsically Disordered Proteins possess an exceptional ability to fold in a template-dependent manner. Intrinsically Disordered Proteins are key players in protein-protein interaction networks being highly abundant among hubs. Furthermore, regions of mRNA which undergo alternative splicing code for Disordered Proteins much more often than they code for structured Proteins. This association of alternative splicing and intrinsic disorder helps Proteins to avoid folding difficulties and provides a novel mechanism for developing tissue-specific protein interaction networks. Numerous Intrinsically Disordered Proteins are associated with such human diseases as cancer, cardiovascular disease, amyloidoses, neurodegenerative diseases, diabetes and others. Our bioinformatics analysis revealed that many human diseases are strongly correlated with Proteins predicted to be Disordered. Contrary to this, we did not find disease associated Proteins to be strongly correlated with absence of disorder. Overall, there is an intriguing interconnection between intrinsic disorder, cell signaling and human diseases, which suggests that protein conformational diseases may result not only from protein misfolding, but also from misidentification and missignaling. Intrinsically Disordered Proteins, such as alpha-synuclein, tau protein, p53, BRCA1 and many other disease-associated hub Proteins represent attractive targets for drugs modulating protein-protein interactions. Therefore, novel strategies for drug discovery are based on Intrinsically Disordered Proteins.
