Pseudo-Improper-Dihedral Model for Intrinsically Disordered Proteins

Mioduszewski, Łukasz; Różycki, Bartosz; Cieplak, Marek

doi:10.1021/acs.jctc.0c00338

Cited by 17 publications

(19 citation statements)

References 75 publications

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“…Here, we propose to use a one-bead-per-residue coarse-grained model [7,8] that captures the most important features of gluten and agrees qualitatively with available data. The main limitation of the model is the usage of time scales that are substantially shorter than those used in the experiments.…”

Section: Introductionsupporting

confidence: 53%

Viscoelastic properties of wheat gluten in a molecular dynamics study

Mioduszewski

Cieplak

2020

Preprint

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Wheat (Triticum spp.) gluten consists mainly of intrinsincally disordered storage proteins (glutenins and gliadins) that can form megadalton-sized networks. These networks are responsible for the unique viscoelastic properties of wheat dough and affect the quality of bread. These properties have not yet been studied by molecular level simulations. Here, we use a newly developed α-C-based coarse-grained model to study ∼ 4000-residue systems. The corresponding time-dependent properties are studied through shear and axial deformations. We measure the response force to the deformation, the number of entanglements and cavities, the size of fluctuations, the number of the inter-chain bonds, etc. Glutenins are shown to influence the mechanics of gluten much more than gliadins. Our simulations are consistent with the existing ideas about gluten elasticity and emphasize the role of entanglements and hydrogen bonding. We also demonstrate that the storage proteins in maize and rice lead to weaker elasticity which points to the unique properties of wheat gluten.

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Section: Introductionsupporting

confidence: 53%

Viscoelastic properties of wheat gluten in a molecular dynamics study

Mioduszewski

Cieplak

2020

Preprint

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“…As detailed in the Supporting Information section: Mathematical Expressions of the Energy Function, the secondary structure potential of the force field is protein-specific and nontransferable. A more predictive secondary structure model may improve the force field’s accuracy in simulating globular structures and in capturing the conformational flexibility of IDPs . Furthermore, we grouped all nonbonded interactions between amino acids into a single contact potential.…”

Section: Discussionmentioning

confidence: 99%

Consistent Force Field Captures Homologue-Resolved HP1 Phase Separation

Latham

Zhang

2021

J. Chem. Theory Comput.

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Many proteins have been shown to function via liquid−liquid phase separation. Computational modeling could offer much needed structural details of protein condensates and reveal the set of molecular interactions that dictate their stability. However, the presence of both ordered and disordered domains in these proteins places a high demand on the model accuracy. Here, we present an algorithm to derive a coarse-grained force field, MOFF, which can model both ordered and disordered proteins with consistent accuracy. It combines maximum entropy biasing, least-squares fitting, and basic principles of energy landscape theory to ensure that MOFF recreates experimental radii of gyration while predicting the folded structures for globular proteins with lower energy. The theta temperature determined from MOFF separates ordered and disordered proteins at 300 K and exhibits a strikingly linear relationship with amino acid sequence composition. We further applied MOFF to study the phase behavior of HP1, an essential protein for posttranslational modification and spatial organization of chromatin. The force field successfully resolved the structural difference of two HP1 homologues despite their high sequence similarity. We carried out large-scale simulations with hundreds of proteins to determine the critical temperature of phase separation and uncover multivalent interactions that stabilize higher-order assemblies. In all, our work makes significant methodological strides to connect theories of ordered and disordered proteins and provides a powerful tool for studying liquid−liquid phase separation with near-atomistic details.

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“…Our rebalancing approach is general and applicable to different types of coarse-grained simulation models of phase separation. There has been much progress in devising coarse-grained [70][71][72] and implicit solvent models 73 of disordered proteins and we envisage that our general approach will make it possible to leverage these developments in coarse-grained modeling of disordered biomolecules for simulations of LLPS and biomolecular condensates. We note that our tuning of the relative strengths of protein-protein and protein-solvent interactions is similar to corrections implemented for highly optimized atomistic protein force fields.…”

Section: Discussionmentioning

confidence: 99%

Simulation of FUS protein condensates with an adapted coarse-grained model

Benayad

Bülow

Stelzl

et al. 2020

Preprint

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Disordered proteins and nucleic acids can condense into droplets that resemble the membraneless organelles observed in living cells. MD simulations offer a unique tool to characterize the molecular interactions governing the formation of these biomolecular condensates, their physico-chemical properties, and the factors controlling their composition and size. However, biopolymer condensation depends sensitively on the balance between different energetic and entropic contributions. Here, we develop a general strategy to fine-tune the potential energy function for molecular dynamics simulations of biopolymer phase separation. We rebalance protein-protein interactions against solvation and entropic contributions to match the excess free energy of transferring proteins between dilute solution and condensate. We illustrate this formalism by simulating liquid droplet formation of the FUS low complexity domain (LCD) with a rebalanced MARTINI model. By scaling the strength of the nonbonded interactions in the coarse-grained MARTINI potential energy function, we map out a phase diagram in the plane of protein concentration and interaction strength. Above a critical scaling factor of αc≈0.6, FUS LCD condensation is observed, where α=1 and 0 correspond to full and repulsive interactions in the MARTINI model, respectively. For a scaling factor α=0.65, we recover the experimental densities of the dilute and dense phases, and thus the excess protein transfer free energy into the droplet and the saturation concentration where FUS LCD condenses. In the region of phase separation, we simulate FUS LCD droplets of four different sizes in stable equilibrium with the dilute phase and slabs of condensed FUS LCD for tens of microseconds, and over one millisecond in aggregate. We determine surface tensions in the range of 0.01-0.4 mN/m from the fluctuations of the droplet shape and from the capillary-wave-like broadening of the interface between the two phases. From the dynamics of the protein end-to-end distance, we estimate shear viscosities from 0.001-0.02 Pa s for the FUS LCD droplets with scaling factors α in the range of 0.625-0.75, where we observe liquid droplets. Significant hydration of the interior of the droplets keeps the proteins mobile and the droplets fluid.

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Pseudo-Improper-Dihedral Model for Intrinsically Disordered Proteins

Cited by 17 publications

References 75 publications

Viscoelastic properties of wheat gluten in a molecular dynamics study

Viscoelastic properties of wheat gluten in a molecular dynamics study

Consistent Force Field Captures Homologue-Resolved HP1 Phase Separation

Simulation of FUS protein condensates with an adapted coarse-grained model

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