Prediction of Hydrodynamic and Other Solution Properties of Partially Disordered Proteins with a Simple, Coarse-Grained Model

2013 ◽  
Vol 9 (3) ◽  
pp. 1678-1685 ◽  
Author(s):  
D. Amorós ◽  
A. Ortega ◽  
J. García de la Torre
Keyword(s):  
Coarse Grained ◽  
Disordered Proteins ◽  
Solution Properties ◽  
Coarse Grained Model ◽  
Partially Disordered Proteins

scholarly journals A predictive coarse-grained model for position-specific effects of post-translational modifications on disordered protein phase separation

2020 ◽  
Author(s):  
T. M. Perdikari ◽  
N. Jovic ◽  
G. L. Dignon ◽  
Y. C. Kim ◽  
N. L. Fawzi ◽  
...  
Keyword(s):  
Amino Acids ◽  
Phase Separation ◽  
Phase Behavior ◽  
Intrinsically Disordered Proteins ◽  
Coarse Grained ◽  
Disordered Proteins ◽  
Post Translational Modifications ◽  
Coarse Grained Model ◽  
Intrinsically Disordered ◽  
Liquid Liquid Phase Separation

AbstractBiomolecules undergo liquid-liquid phase separation (LLPS) resulting in the formation of multicomponent protein-RNA membraneless organelles in cells. However, the physiological and pathological role of post translational modifications (PTMs) on the biophysics of phase behavior is only beginning to be probed. To study the effect of PTMs on LLPS in silico, we extend our transferable coarse-grained model of intrinsically disordered proteins to include phosphorylated and acetylated amino acids. Using the parameters for modified amino acids available for fixed charge atomistic forcefields, we parameterize the size and atomistic hydropathy of the coarse-grained modified amino acid beads, and hence the interactions between the modified and natural amino acids. We then elucidate how the number and position of phosphorylated and acetylated residues alter the protein’s single chain compactness and its propensity to phase separate. We show that both the number and the position of phosphorylated threonines/serines or acetylated lysines can serve as a molecular on/off switch for phase separation in the well-studied disordered regions of FUS and DDX3X, respectively. We also compare modified residues to their commonly used PTM mimics for their impact on chain properties. Importantly, we show that the model can predict and capture experimentally measured differences in the phase behavior for position-specific modifications, showing that the position of modifications can dictate phase separation. In sum, this model will be useful for studying LLPS of post-translationally modified intrinsically disordered proteins and predicting how modifications control phase behavior with position-specific resolution.Statement of SignificancePost-translational modifications are important regulators of liquid-liquid phase separation (LLPS) which drives the formation of biomolecular condensates. Theoretical methods can be used to characterize the biophysical properties of intrinsically disordered proteins (IDPs). Our recent framework for molecular simulations using a Cα-centered coarse-grained model can predict the effect of various perturbations such as mutations (Dignon et al. PloS Comput. Biol, 2018) and temperature (Dignon et al, ACS Cent. Sci., 2019) on LLPS. Here, we expand this framework to incorporate modified residues like phosphothreonine, phosphoserine and acetylysine. This model will prove useful for simulating the phase separation of post-translationally modified IDPs and predicting how position-specific modifications can control phase behavior across the large family of proteins known to be phosphorylated and acetylated.

scholarly journals Testing the transferability of a coarse-grained model to intrinsically disordered proteins

2015 ◽  
Vol 17 (47) ◽  
pp. 31741-31749 ◽  
Author(s):  
Gil O. Rutter ◽  
Aaron H. Brown ◽  
David Quigley ◽  
Tiffany R. Walsh ◽  
Michael P. Allen
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Coarse Grained ◽  
Disordered Proteins ◽  
Coarse Grained Model ◽  
Intrinsically Disordered

The coarse-grained PLUM model is shown to capture structural and dimerization behaviour of the intrinsically disordered biomineralisation peptide n16N.

scholarly journals Disordered peptide chains in an α-C-based coarse-grained model

2018 ◽  
Vol 20 (28) ◽  
pp. 19057-19070 ◽  
Author(s):  
Łukasz Mioduszewski ◽  
Marek Cieplak
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Coarse Grained ◽  
Disordered Proteins ◽  
Dynamical Model ◽  
Coarse Grained Model ◽  
Intrinsically Disordered

A one-bead-per-residue coarse-grained dynamical model for intrinsically disordered proteins is proposed. It distinguishes between the backbone and sidechain interactions.

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