Gō model revisited

Takada, Shoji

doi:10.2142/biophysico.16.0_248

Cited by 50 publications

(67 citation statements)

References 77 publications

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“…Coarse-grained models with different levels of structural resolution have a long history and continue to be used in molecular simulation studies of protein folding [35]. Structurebased models such as the Gō model (reviewed in [36]) are particularly popular because they lead to smooth free energy landscapes, and encapsulate the importance of native structure as a driver of protein folding mechanisms and kinetics [37]. Since the Gō model is native-centric, it is natural to expect that simulated folding behaviour may be sensitive to the exact set of atomic coordinates that define the native structure.…”

Section: Discussionmentioning

confidence: 99%

The folding space of protein β2-microglobulin is modulated by a single disulfide bridge

Morand

Nunes

Faísca

2021

Preprint

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Protein beta-2-microglobulin (β2m) is classically considered the causative agent of dialysis related amyloidosis (DRA), a conformational disorder that affects patients undergoing long-term hemodialysis. Together with the wild type form, the ΔN6 structural variant, and the D76N mutant, have been extensively used as model systems of β2m aggregation. In all of them, the native structure is stabilized by a disulfide bridge between the sulphur atoms of the cysteine residues 25 (at B strand) and 80 (at F strand), which has been considered fundamental in β2m fibrillogenesis. Here, we use extensive Discrete Molecular Dynamics simulations of a full atomistic structure-based model to explore the role of this disulfide bridge as a modulator of the folding space of β2m. In particular, by considering different models for the disulfide bridge, we explore the thermodynamics of the folding transition, and the formation of intermediate states that may have the potential to trigger the aggregation cascade. Our results show that the dissulfide bridge affects folding transition and folding thermodynamics of the considered model systems, although to different extents. In particular, when the interaction between the sulphur atoms is stabilized relative to the other intramolecular interactions, or even locked (i.e. permanently established), the WT form populates an intermediate state featuring a well preserved core, and two unstructured termini, which was previously detected only for the D76N mutant. The formation of this intermediate state may have important implications in our understanding of β2m fibrillogenesis.

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Section: Discussionmentioning

confidence: 99%

The folding space of protein β2-microglobulin is modulated by a single disulfide bridge

Morand

Nunes

Faísca

2021

Preprint

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“…In both cases the strength of the interaction parameters is independent of the residues' chemical detail; this condition, together with the C α mapping prescription, was later relaxed in subsequent generalizations, which relied on more chemicallyrealistic functional forms for the interactions (Karanicolas and Brooks, 2002), as well as quasi-atomistic descriptions of the biomolecule (Whitford et al, 2009). Due to their extreme simplicity and flexibility, GLMs have a long and successful history in the field of protein folding (Hills and Brooks, 2009;Hu et al, 2017;Takada, 2019). Furthermore, the original native-centric standpoint was later extended to account for the presence of multiple (meta)stable conformational basins, allowing transitions between them at greatly reduced computational cost (Best et al, 2005;Okazaki et al, 2006).…”

Section: Implicit Solvent Coarse-grained Modelsmentioning

confidence: 99%

“…A notable example of this second class of implicit solvent CG models is represented by structure-based ones, such as Gō-like models (GLM) ( Hills and Brooks, 2009 ; Takada, 2019 ) or elastic network models (ENM) ( Sanejouand, 2013 ; Togashi and Flechsig, 2018 ). Here, the external macroscopic input involved in the construction of the effective CG potential is the static, either stable or metastable, three-dimensional spatial conformation assumed by the protein of interest.…”

Section: Coarse-grained Modeling: Resolution Levelmentioning

confidence: 99%

“…Due to their extreme simplicity and flexibility, GLMs have a long and successful history in the field of protein folding ( Hills and Brooks, 2009 ; Hu et al, 2017 ; Takada, 2019 ). Furthermore, the original native-centric standpoint was later extended to account for the presence of multiple (meta)stable conformational basins, allowing transitions between them at greatly reduced computational cost ( Best et al, 2005 ; Okazaki et al, 2006 ).…”

Section: Coarse-grained Modeling: Resolution Levelmentioning

confidence: 99%

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From System Modeling to System Analysis: The Impact of Resolution Level and Resolution Distribution in the Computer-Aided Investigation of Biomolecules

Giulini

Rigoli

Mattiotti

et al. 2021

Front. Mol. Biosci.

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The ever increasing computer power, together with the improved accuracy of atomistic force fields, enables researchers to investigate biological systems at the molecular level with remarkable detail. However, the relevant length and time scales of many processes of interest are still hardly within reach even for state-of-the-art hardware, thus leaving important questions often unanswered. The computer-aided investigation of many biological physics problems thus largely benefits from the usage of coarse-grained models, that is, simplified representations of a molecule at a level of resolution that is lower than atomistic. A plethora of coarse-grained models have been developed, which differ most notably in their granularity; this latter aspect determines one of the crucial open issues in the field, i.e. the identification of an optimal degree of coarsening, which enables the greatest simplification at the expenses of the smallest information loss. In this review, we present the problem of coarse-grained modeling in biophysics from the viewpoint of system representation and information content. In particular, we discuss two distinct yet complementary aspects of protein modeling: on the one hand, the relationship between the resolution of a model and its capacity of accurately reproducing the properties of interest; on the other hand, the possibility of employing a lower resolution description of a detailed model to extract simple, useful, and intelligible information from the latter.

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“…The methodology developed here is especially useful for coarse-grained modeling of biomolecules, such as RNA nanotubes, that possess very large numbers of nucleotides in the nucleic acid. Prior studies were performed on such structures as 16-RNA molecules and 10-RNA protein complexes and some others by using generic sets of coarse-grained model parameters, with details given in [ 40 , 41 , 42 ], but not on RNA nanotubes.…”

Section: Introductionmentioning

confidence: 99%

Coarse-Grained Models of RNA Nanotubes for Large Time Scale Studies in Biomedical Applications

2020

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In order to describe the physical properties of large time scale biological systems, coarse-grained models play an increasingly important role. In this paper we develop Coarse-Grained (CG) models for RNA nanotubes and then, by using Molecular Dynamics (MD) simulation, we study their physical properties. Our exemplifications include RNA nanotubes of 40 nm long, equivalent to 10 RNA nanorings connected in series. The developed methodology is based on a coarse-grained representation of RNA nanotubes, where each coarse bead represents a group of atoms. By decreasing computation cost, this allows us to make computations feasible for realistic structures of interest. In particular, for the developed coarse-grained models with three bead approximations, we calculate the histograms for the bond angles and the dihedral angles. From the dihedral angle histograms, we analyze the characteristics of the links used to build the nanotubes. Furthermore, we also calculate the bead distances along the chains of RNA strands in the nanoclusters. The variations in these features with the size of the nanotube are discussed in detail. Finally, we present the results on the calculation of the root mean square deviations for a developed RNA nanotube to demonstrate the equilibration of the systems for drug delivery and other biomedical applications such as medical imaging and tissue engineering.

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Gō model revisited

Cited by 50 publications

References 77 publications

The folding space of protein β2-microglobulin is modulated by a single disulfide bridge

The folding space of protein β2-microglobulin is modulated by a single disulfide bridge

From System Modeling to System Analysis: The Impact of Resolution Level and Resolution Distribution in the Computer-Aided Investigation of Biomolecules

Coarse-Grained Models of RNA Nanotubes for Large Time Scale Studies in Biomedical Applications

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