scholarly journals Understanding the Phase Behavior of Coarse-Grained Model Lipid Bilayers through Computational Calorimetry

2012 ◽  
Vol 116 (5) ◽  
pp. 1551-1569 ◽  
Author(s):  
Jocelyn M. Rodgers ◽  
Jesper Sørensen ◽  
Frédérick J.-M. de Meyer ◽  
Birgit Schiøtt ◽  
Berend Smit
Keyword(s):  
Phase Behavior ◽  
Lipid Bilayers ◽  
Coarse Grained ◽  
Coarse Grained Model

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 Coarse-grained Force Fields from the Perspective of Statistical Mechanics: Better Understanding the Origins of a MARTINI Hangover

2020 ◽  
Author(s):  
Zack Jarin ◽  
James Newhouse ◽  
Gregory A. Voth
Keyword(s):  
Statistical Mechanics ◽  
Lipid Bilayers ◽  
Potential Of Mean Force ◽  
Distribution Functions ◽  
Coarse Grained ◽  
Test Case ◽  
Top Down ◽  
Coarse Grained Model ◽  
Potentials Of Mean Force ◽  
Dynamics Models

AbstractThe popular MARTINI coarse-grained model is used as a test case to analyze the adherence of top-down coarse-grained molecular dynamics models (i.e., models primarily parameterized to match experimental results) to the known features of statistical mechanics for the underlying all-atom representations. Specifically, the temperature dependence of various pair distribution functions, and hence their underlying potentials of mean force via the reversible work theorem, are compared between MARTINI 2.0, Dry MARTINI, and all-atom simulations mapped onto equivalent coarse-grained sites for certain lipid bilayers. It is found that the MARTINI models do not completely capture the lipid structure seen in atomistic simulations as projected onto the coarse-grained mappings, and that issues of accuracy and temperature transferability arise due to an incorrect enthalpy-entropy decomposition of these potentials of mean force. The potential of mean force for the association of two amphipathic helices in a lipid bilayer is also calculated and, especially at shorter ranges, the MARTINI and all-atom projection results differ substantially. The former is much less repulsive and hence will lead to a higher probability of MARTINI helix association in the MARTINI bilayer than occurs in the actual all-atom case. Additionally, the bilayer height fluctuation spectra are calculated for the MARTINI model and – compared to the all-atom results – it is found that the magnitude of thermally averaged amplitudes at intermediate length scales is quite different, pointing to a number of possible consequences for realistic modeling of membrane processes. Taken as a whole, the results presented here can point the way for future coarse-grained model parameterization efforts that might bring top-down coarse-grained models into better agreement with the statistical mechanics of the actual all-atom systems they aspire to represent.

scholarly journals Derivation of coarse-grained simulation models of chlorophyll molecules in lipid bilayers for applications in light harvesting systems

2015 ◽  
Vol 17 (34) ◽  
pp. 22054-22063 ◽  
Author(s):  
Ananya Debnath ◽  
Sabine Wiegand ◽  
Harald Paulsen ◽  
Kurt Kremer ◽  
Christine Peter
Keyword(s):  
Lipid Bilayers ◽  
Light Harvesting ◽  
Simulation Models ◽  
Coarse Grained ◽  
Light Harvesting Complex ◽  
Green Plants ◽  
Coarse Grained Model ◽  
Multi Scale ◽  
Harvesting Systems ◽  
Association Behavior

A coarse-grained model is derived for chlorophyll molecules in lipid bilayers using a multi-scale simulation ansatz aiming to understand the association behavior of the light harvesting complex (LHCII) of green plants.

Artifacts in dynamical simulations of coarse-grained model lipid bilayers

2005 ◽  
Vol 122 (20) ◽  
pp. 204901 ◽  
Author(s):  
Ask F. Jakobsen ◽  
Ole G. Mouritsen ◽  
Gerhard Besold
Keyword(s):  
Lipid Bilayers ◽  
Coarse Grained ◽  
Coarse Grained Model ◽  
Dynamical Simulations

scholarly journals Sequence determinants of protein phase behavior from a coarse-grained model

2018 ◽  
Vol 14 (1) ◽  
pp. e1005941 ◽  
Author(s):  
Gregory L. Dignon ◽  
Wenwei Zheng ◽  
Young C. Kim ◽  
Robert B. Best ◽  
Jeetain Mittal
Keyword(s):  
Phase Behavior ◽  
Coarse Grained ◽  
Coarse Grained Model

scholarly journals Peroxidised phospholipid bilayers: insight from coarse-grained molecular dynamics simulations

Soft Matter ◽  
2016 ◽  
Vol 12 (1) ◽  
pp. 263-271 ◽  
Author(s):  
Yachong Guo ◽  
Vladimir A. Baulin ◽  
Fabrice Thalmann
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Lipid Bilayers ◽  
Phospholipid Bilayers ◽  
Coarse Grained ◽  
Coarse Grained Model ◽  
Dynamics Simulations ◽  
Coarse Grained Molecular Dynamics

We introduce a coarse-grained model for hydroperoxide lipid bilayers.

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