Filamentous Aggregates of Tau Proteins Fulfil Standard Amyloid Criteria Provided by the Fuzzy Oil Drop (FOD) Model

Dułak, Dawid; Gadzała, Małgorzata; Banach, Mateusz; Ptak, Magdalena; Wiśniowski, Zdzisław; Konieczny, Leszek; Roterman, Irena

doi:10.3390/ijms19102910

Cited by 23 publications

(21 citation statements)

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“…In this way, a band micelle is obtained, which is generated by amyloid proteins. Amyloids represent a structural form with a hydrophobic core in the form of a tape running along the long axis of fibril surrounding it with better or worse matched bands with low hydrophobicity [48][49][50][51][52]. Thus, amyloids are a synergy that is different from the native form, leading to an alternative solution to the impact and presence of a polar aquatic environment.…”

Section: Discussionmentioning

confidence: 99%

“…The current analysis is to check the degree of universality of this approach including correctly folded proteins. The structure of the hydrophobic core-its degree of compliance with the idealized distribution-is determined using a model called the fuzzy oil drop model [47][48][49][50][51][52][53][54][55][56][57], in which the idealized distribution of hydrophobicity (T) is expressed using a 3D Gaussian distribution, which is spread over the body of the protein (values of the σ-x, α-y and α-z parameters are selected specifically for a given protein). On the other hand, the actual distribution of hydrophobicity (O) is assessed resulting from the distribution of so-called effective atoms (the average position of atoms included in a given amino acid) and intrinsic hydrophobicity, which is constant for a given amino acid.…”

Section: Model Of Amino Acid Conformation Analysis In the Chainmentioning

confidence: 99%

“…The work shows that the structure of the hydrophobic core is the result of general molecular synergy expressed in the organization of the distribution of hydrophobicity which is the share of all components. This synergy is particularly evident in changes known as amyloid transformation [48][49][50][51].…”

Section: Introductionmentioning

confidence: 99%

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Alternative Hydrophobic Core in Proteins—The Effect of Specific Synergy

et al. 2020

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Proteins with a high degree of sequence similarity representing different structures provide a key to understand how protein sequence codes for 3D structure. An analysis using the fuzzy oil drop model was carried out on two pairs of proteins with different secondary structures and with high sequence identities. It has been shown that distributions of hydrophobicity for these proteins are approximated well using single 3D Gaussian function. In other words, the similar sequences fold into different 3D structures, however, alternative structures also have symmetric and monocentric hydrophobic cores. It should be noted that a significant change in the helical to beta-structured form in the N-terminal section takes places in the fragment much preceding the location of the mutated regions. It can be concluded that the final structure is the result of a complicated synergy effect in which the whole chain participates simultaneously.

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Section: Discussionmentioning

confidence: 99%

Section: Model Of Amino Acid Conformation Analysis In the Chainmentioning

confidence: 99%

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Alternative Hydrophobic Core in Proteins—The Effect of Specific Synergy

et al. 2020

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“…The fuzzy oil drop model treats amyloids as ribbonlike micelles (in contrast to spherical micelles, which represent globular proteins) (Kalinowska et al, 2017). The presence of short fragments, whose local distribution of hydrophobicity opposes the theoretical model, results from the systemic inability of the amyloid peptide to attain a spherical conformation (Dułak et al, 2018a;Dułak et al, 2018b). This locally suboptimal distribution is compensated by the isolation of discordant fragments in the structure of a ribbon-like micelle.…”

Section: Discussionmentioning

confidence: 99%

“…The set includes titin as a representative of a class of strongly accordant proteins (Banach et al, 2014a;Banach et al, 2014b), along with several amyloids whose structures can be found in PDB. The latter facilitate the analysis of the distribution of hydrophobic, electrostatic and vdW interactions in amyloids (note that the distribution of hydrophobicity in amyloids is extensively discussed in several other publications: (Dułak et al, 2018a;Dułak et al, 2018b)). Transthyretin was selected for this study due to its strong propensity for amyloid transformation (Lim et al, 2016).…”

Section: Methodsmentioning

confidence: 99%

Internal force field in selected proteins

et al. 2019

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The fuzzy oil drop model suggests that the tertiary conformation of a protein -particularly a globular one -can be likened to a spherical micelle. During the folding process, hydrophilic residues are exposed on the surface, while hydrophobic residues are retained inside the protein. The resulting hydrophobicity distribution can be mathematically modeled as a 3D Gaussian. The fuzzy oil drop model is strikingly effective in explaining the properties of type II antifreeze proteins and fast-folding proteins, as well as a vast majority of autonomous protein domains. This work aims to determine whether similar mechanisms apply to other types of nonbonding interactions. Our analysis indicates that electrostatic and van der Waals forces do not conform to the Gaussian pattern. The study involves a reference protein (titin) which shows a high agreement between the observed distribution of hydrophobicity and the theoretical (Gaussian) distribution, a selection of amyloid structures derived from the Protein Data Bank, as well as transthyretin -a protein known for its susceptibility to amyloid transformation.

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Recent Computational Approaches on Mechanical Behavior of Axonal Cytoskeletal Components of Neuron: A Brief Review

Khan

Hasan

Mahmud

et al. 2020

Multiscale Sci. Eng.

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Axonal cytoskeletal components of neuron have been studied and modeled by using different approaches. The axonal cytoskeleton comprises of microtubules (MTs), which mostly control the overall property and behavior of axon. However, MTs contain crosslinks which are MT associated proteins (mainly tau proteins), intermediate filaments (mainly neurofilaments or NFs in case of brain axon), and microfilaments (MFs). Due to the micrometer level length scale of the components, experimental approaches such as microscopy are inconvenient. In this regard, several computational approaches, such as fully atomistic molecular dynamics (MD) simulation, coarse grained (CG) simulation, or finite element analysis (FEA) can be considered reasonable approaches for observing the behavior of the cytoskeletal components and determining their mechanical properties. Among the cytoskeletal components, MTs and MFs are well studied, but the behavior of taus and NFs are not studied comprehensively. Over the last two decades, the computational approaches have been improved manifold to determine and analyze numerous aspects of cytoskeletal components. Due to structurally disordered nature of tau and NF we lack sufficient literature on these components, almost all the structural and behavioral aspects have been analyzed in depth for MT and MF -for which computational studies have played vital role. This study attempts to discuss the current scenario of these computational approaches performed on cytoskeletal components, as well as recent advancements. It attempts to benchmark the current capability of computational approaches to find out properties, behavior, and dynamics of cytoskeletal components, which is required to further advance using similar maneuvers. Importantly, we also pinpoint the possibilities of future studies through which the current limitations in the tau and NF territories can be effectively addressed.

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Filamentous Aggregates of Tau Proteins Fulfil Standard Amyloid Criteria Provided by the Fuzzy Oil Drop (FOD) Model

Cited by 23 publications

References 81 publications

Alternative Hydrophobic Core in Proteins—The Effect of Specific Synergy

Alternative Hydrophobic Core in Proteins—The Effect of Specific Synergy

Internal force field in selected proteins

Recent Computational Approaches on Mechanical Behavior of Axonal Cytoskeletal Components of Neuron: A Brief Review

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