scholarly journals AWSEM-IDP: A Coarse-Grained Force Field for Intrinsically Disordered Proteins

2018 ◽  
Vol 122 (49) ◽  
pp. 11115-11125 ◽  
Author(s):  
Hao Wu ◽  
Peter G. Wolynes ◽  
Garegin A. Papoian
Keyword(s):  
Force Field ◽  
Intrinsically Disordered Proteins ◽  
Coarse Grained ◽  
Disordered Proteins ◽  
Intrinsically Disordered

scholarly journals Identifying sequence perturbations to an intrinsically disordered protein that determine its phase-separation behavior

2020 ◽  
Vol 117 (21) ◽  
pp. 11421-11431 ◽  
Author(s):  
Benjamin S. Schuster ◽  
Gregory L. Dignon ◽  
Wai Shing Tang ◽  
Fleurie M. Kelley ◽  
Aishwarya Kanchi Ranganath ◽  
...  
Keyword(s):  
Phase Separation ◽  
Intrinsically Disordered Proteins ◽  
Lipid Membrane ◽  
Coarse Grained ◽  
Disordered Proteins ◽  
Sequence Features ◽  
Intrinsically Disordered ◽  
Arginine Residues

Phase separation of intrinsically disordered proteins (IDPs) commonly underlies the formation of membraneless organelles, which compartmentalize molecules intracellularly in the absence of a lipid membrane. Identifying the protein sequence features responsible for IDP phase separation is critical for understanding physiological roles and pathological consequences of biomolecular condensation, as well as for harnessing phase separation for applications in bioinspired materials design. To expand our knowledge of sequence determinants of IDP phase separation, we characterized variants of the intrinsically disordered RGG domain from LAF-1, a model protein involved in phase separation and a key component of P granules. Based on a predictive coarse-grained IDP model, we identified a region of the RGG domain that has high contact probability and is highly conserved between species; deletion of this region significantly disrupts phase separation in vitro and in vivo. We determined the effects of charge patterning on phase behavior through sequence shuffling. We designed sequences with significantly increased phase separation propensity by shuffling the wild-type sequence, which contains well-mixed charged residues, to increase charge segregation. This result indicates the natural sequence is under negative selection to moderate this mode of interaction. We measured the contributions of tyrosine and arginine residues to phase separation experimentally through mutagenesis studies and computationally through direct interrogation of different modes of interaction using all-atom simulations. Finally, we show that despite these sequence perturbations, the RGG-derived condensates remain liquid-like. Together, these studies advance our fundamental understanding of key biophysical principles and sequence features important to phase separation.

scholarly journals Rescuing the Over-Collapse of Intrinsically Disordered Proteins using a Force Field Derived by a New Paradigm

2016 ◽  
Vol 110 (3) ◽  
pp. 556a
Author(s):  
Davide Mercadante ◽  
Sigrid Milles ◽  
Gustavo Fuertes ◽  
Dmitri Svergun ◽  
Edward A. Lemke ◽  
...  
Keyword(s):  
Force Field ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
New Paradigm ◽  
Intrinsically Disordered

scholarly journals CHARMM36: An Improved Force Field for Folded and Intrinsically Disordered Proteins

2017 ◽  
Vol 112 (3) ◽  
pp. 175a-176a ◽  
Author(s):  
Jing Huang ◽  
Sarah Rauscher ◽  
Grzegorz Nawrocki ◽  
Ting Ran ◽  
Michael Feig ◽  
...  
Keyword(s):  
Force Field ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Intrinsically Disordered

scholarly journals Structural Ensembles of Intrinsically Disordered Proteins Depend Strongly on Force Field

2014 ◽  
Vol 106 (2) ◽  
pp. 271a ◽  
Author(s):  
Sarah Rauscher ◽  
Vytautas Gapsys ◽  
Andreas Volkhardt ◽  
Christian Blau ◽  
Bert L. de Groot ◽  
...  
Keyword(s):  
Force Field ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Intrinsically Disordered ◽  
Structural Ensembles

scholarly journals Bayesian inference of protein ensembles from SAXS data

2016 ◽  
Vol 18 (8) ◽  
pp. 5832-5838 ◽  
Author(s):  
L. D. Antonov ◽  
S. Olsson ◽  
W. Boomsma ◽  
T. Hamelryck
Keyword(s):  
Bayesian Inference ◽  
Force Field ◽  
Intrinsically Disordered Proteins ◽  
Probabilistic Method ◽  
Disordered Proteins ◽  
Saxs Data ◽  
Intrinsically Disordered ◽  
Protein Ensembles

A probabilistic method infers ensembles of intrinsically disordered proteins (IDPs) by combining SAXS data with a force field.

scholarly journals Modelling the structure and interactions of intrinsically disordered peptides with multiple-replica, metadynamics-based sampling methods and force-field combinations

2021 ◽  
Author(s):  
Lunna Li ◽  
Tommaso Casalini ◽  
Paolo Arosio ◽  
Matteo Salvalaglio
Keyword(s):  
Force Field ◽  
Sampling Method ◽  
Intrinsically Disordered Proteins ◽  
Thermodynamic Characteristics ◽  
Building Blocks ◽  
Disordered Proteins ◽  
Intrinsically Disordered ◽  
Self Association ◽  
Disordered Peptides

Intrinsically disordered proteins (IDPs) play a key role in many biological processes, including the formation of biomolecular condensates within cells. A detailed characterization of their configurational ensemble and structure-function paradigm is crucial for understanding their biological activity and for exploiting them as building blocks in material sciences. In this work, we incorporate bias-exchange metadynamics and parallel-tempering well-tempered metadynamics with CHARMM36m and CHARMM22* to explore the structural and thermodynamic characteristics of a short archetypal disordered sequence derived from a DEAD-box protein. The conformational landscapes emerging from our simulations are largely congruent across methods and forcefields. Nevertheless, differences in fine details emerge from varying forcefield/sampling method combinations. For this protein, our analysis identifies features that help to explain the low propensity of this sequence to undergo self-association in vitro, which can be common to all force-field/sampling method combinations. Overall, our work demonstrates the importance of using multiple force-field/enhanced sampling method combinations for accurate structural and thermodynamic information in the study of general disordered proteins.

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