scholarly journals Exploring Curated Conformational Ensembles of Intrinsically Disordered Proteins in the Protein Ensemble Database

2021 ◽  
Vol 1 (7) ◽  
Author(s):  
Federica Quaglia ◽  
Tamas Lazar ◽  
András Hatos ◽  
Peter Tompa ◽  
Damiano Piovesan ◽  
...  
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Conformational Ensembles ◽  
Intrinsically Disordered

Molecular simulations of protein disorderThis paper is one of a selection of papers published in this special issue entitled “Canadian Society of Biochemistry, Molecular & Cellular Biology 52nd Annual Meeting — Protein Folding: Principles and Diseases” and has undergone the Journal's usual peer review process.

2010 ◽  
Vol 88 (2) ◽  
pp. 269-290 ◽  
Author(s):  
Sarah Rauscher ◽  
Régis Pomès
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Peer Review Process ◽  
Structural Heterogeneity ◽  
Disordered Proteins ◽  
Cellular Biology ◽  
Protein Disorder ◽  
Conformational Ensembles ◽  
Intrinsically Disordered ◽  
Simulation Techniques ◽  
Selection Of

Protein disorder is abundant in proteomes throughout all kingdoms of life and serves many biologically important roles. Disordered states of proteins are challenging to study experimentally due to their structural heterogeneity and tendency to aggregate. Computer simulations, which are not impeded by these properties, have recently emerged as a useful tool to characterize the conformational ensembles of intrinsically disordered proteins. In this review, we provide a survey of computational studies of protein disorder with an emphasis on the interdisciplinary nature of these studies. The application of simulation techniques to the study of disordered states is described in the context of experimental and bioinformatics approaches. Experimental data can be incorporated into simulations, and simulations can provide predictions for experiment. In this way, simulations have been integrated into the existing methodologies for the study of disordered state ensembles. We provide recent examples of simulations of disordered states from the literature and our own work. Throughout the review, we emphasize important predictions and biophysical understanding made possible through the use of simulations. This review is intended as both an overview and a guide for structural biologists and theoretical biophysicists seeking accurate, atomic-level descriptions of disordered state ensembles.

scholarly journals Nanopores to Interrogate the Conformational Ensembles of Intrinsically Disordered Proteins on a Single-Molecule Level

2020 ◽  
Vol 118 (3) ◽  
pp. 214a
Author(s):  
Saurabh Awasthi ◽  
Jared Houghtaling ◽  
Cuifeng Ying ◽  
Aziz Fennouri ◽  
Ivan Shorubalko ◽  
...  
Keyword(s):  
Single Molecule ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Single Molecule Level ◽  
Conformational Ensembles ◽  
Intrinsically Disordered

scholarly journals Information theoretic measures for quantifying sequence–ensemble relationships of intrinsically disordered proteins

2019 ◽  
Vol 32 (4) ◽  
pp. 191-202 ◽  
Author(s):  
Megan C Cohan ◽  
Kiersten M Ruff ◽  
Rohit V Pappu
Keyword(s):  
Intrinsically Disordered Proteins ◽  
De Novo ◽  
Disordered Proteins ◽  
Specific Sequence ◽  
Information Theoretic ◽  
Conformational Ensembles ◽  
Intrinsically Disordered ◽  
Information Theoretic Measures ◽  
Modulating Functions ◽  
The Impact

Abstract Intrinsically disordered proteins (IDPs) contribute to a multitude of functions. De novo design of IDPs should open the door to modulating functions and phenotypes controlled by these systems. Recent design efforts have focused on compositional biases and specific sequence patterns as the design features. Analysis of the impact of these designs on sequence-function relationships indicates that individual sequence/compositional parameters are insufficient for describing sequence-function relationships in IDPs. To remedy this problem, we have developed information theoretic measures for sequence–ensemble relationships (SERs) of IDPs. These measures rely on prior availability of statistically robust conformational ensembles derived from all atom simulations. We show that the measures we have developed are useful for comparing sequence-ensemble relationships even when sequence is poorly conserved. Based on our results, we propose that de novo designs of IDPs, guided by knowledge of their SERs, should provide improved insights into their sequence–ensemble–function relationships.

scholarly journals Distance-Based Metrics for Comparing Conformational Ensembles of Intrinsically Disordered Proteins

2020 ◽  
Vol 118 (12) ◽  
pp. 2952-2965
Author(s):  
Tamas Lazar ◽  
Mainak Guharoy ◽  
Wim Vranken ◽  
Sarah Rauscher ◽  
Shoshana J. Wodak ◽  
...  
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Conformational Ensembles ◽  
Intrinsically Disordered

scholarly journals Single-molecule spectroscopy of unfolded proteins and chaperonin action

2014 ◽  
Vol 395 (7-8) ◽  
pp. 689-698 ◽  
Author(s):  
Hagen Hofmann
Keyword(s):  
Single Molecule ◽  
Molecular Chaperones ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Unfolded Proteins ◽  
Conformational Ensembles ◽  
Intrinsically Disordered ◽  
Cellular Environment ◽  
Quantitative Understanding ◽  
Polypeptide Chains

Abstract In the past decade, single-molecule fluorescence techniques provided important insights into the structure and dynamics of proteins. In particular, our understanding of the heterogeneous conformational ensembles of unfolded and intrinsically disordered proteins (IDPs) improved substantially by a combination of FRET-based single-molecule techniques with concepts from polymer physics. A complete knowledge of the forces that act in unfolded polypeptide chains will not only be important to understand the initial steps of protein folding reactions, but it will also be crucial to rationalize the coupling between ligand-binding and folding of IDPs, and the interaction of denatured proteins with molecular chaperones in the crowded cellular environment. Here, I give a personalized review of some of the key findings from my own research that contributed to a more quantitative understanding of unfolded proteins and their interactions with molecular chaperones.

scholarly journals Integrating multiple experimental data to determine conformational ensembles of an intrinsically disordered protein

2020 ◽  
Author(s):  
Gregory-Neal W. Gomes ◽  
Mickaël Krzeminski ◽  
Ashley Namini ◽  
Erik. W. Martin ◽  
Tanja Mittag ◽  
...  
Keyword(s):  
Experimental Data ◽  
Single Molecule ◽  
Intrinsically Disordered Proteins ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Intrinsically Disordered Protein ◽  
Disordered Proteins ◽  
Saxs Data ◽  
Conformational Ensembles ◽  
Intrinsically Disordered

AbstractIntrinsically disordered proteins (IDPs) have fluctuating heterogeneous conformations, which makes structural characterization challenging, but of great interest, since their conformational ensembles are the link between their sequences and functions. An accurate description of IDP conformational ensembles depends crucially on the amount and quality of the experimental data, how it is integrated, and if it supports a consistent structural picture. We have used an integrative modelling approach to understand how conformational restraints imposed by the most common structural techniques for IDPs: Nuclear Magnetic Resonance (NMR) spectroscopy, Small-angle X-ray Scattering (SAXS), and single-molecule Förster Resonance Energy Transfer (smFRET) reach concordance on structural ensembles for Sic1 and phosphorylated Sic1 (pSic1). To resolve apparent discrepancies between smFRET and SAXS, we integrated SAXS data with non-smFRET (NMR) data and reserved the new smFRET data for Sic1 and pSic1 as an independent validation. The consistency of the SAXS/NMR restrained ensembles with smFRET, which was not guaranteed a priori, indicates that the perturbative effects of NMR or smFRET labels on the Sic1 and pSic1 ensembles are minimal. Furthermore, the mutual agreement with such a diverse set of experimental data suggest that details of the generated ensembles can now be examined with a high degree of confidence to reveal distinguishing features of Sic1 vs. pSic1. From the experimentally well supported ensembles, we find they are consistent with independent biophysical models of Sic1’s ultrasensitive binding to its partner Cdc4. Our results underscore the importance of integrative modelling in calculating and drawing biological conclusions from IDP conformational ensembles.

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