Molecular Insights into the Self‐Assembly of Block Copolymer Suckerin Polypeptides into Nanoconfined β‐Sheets

Liu, Yuying; Wang, Ying; Tong, Chaohui; Wei, Guanghong; Ding, Feng; Sun, Yunxiang

doi:10.1002/smll.202202642

Cited by 13 publications

(15 citation statements)

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“…Besides, we have calculated the probabilities of β-sheet oligomer size and β-sheet size of PHF6 in two systems. Here, the β-sheet oligomer size is defined by the total number of β-strands in a β-sheet oligomer, and β-sheet size refers to the number of strands in an n -stranded β-sheet. , It can be seen from Figure d that PHF6 predominantly aggregates into oligomers with the number of β-strands of 4–8, and the large size (9–10) of β-sheet oligomers can also be observed in the PHF6 system. When Y310 is phosphorylated, the probability of β-sheet oligomers with four β-strands is obviously increased, and the large size of β-sheet oligomers is disappeared.…”

Section: Resultsmentioning

confidence: 99%

“…A H-bond was considered to be formed if the distance between the H-bonding donor D and the acceptor A was less than 0.35 nm and the angle of D–H···A was greater than 150°. Following our previous studies, the average β-sheet size was weighed according to the size of each β-sheet. , The potential of mean force (PMF) was constructed using the equation F = − RT ln P ( x , y ), where P ( x , y ) is the probability of a conformation having a certain value of two selected reaction coordinates x and y . The Daura analysis method was applied to cluster the sampled conformations using a Cα root-mean-square deviation (Cα-rmsd) cutoff of 0.45 nm .…”

Section: Methodsmentioning

confidence: 99%

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Atomistic Insights into the Inhibitory Mechanism of Tyrosine Phosphorylation against the Aggregation of Human Tau Fragment PHF6

et al. 2023

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Abnormal aggregation of the microtubule-associated protein tau into intracellular fibrillary inclusions is characterized as the hallmark of tauopathies, including Alzheimer’s disease and chronic traumatic encephalopathy. The hexapeptide 306VQIVYK311 (PHF6) of R3 plays an important role in the aggregation of tau. Recent experimental studies reported that phosphorylation of residue tyrosine 310 (Y310) could decrease the propensity of PHF6 to form fibrils and inhibit tau aggregation. However, the underlying inhibitory mechanism is not well understood. In this work, we systematically investigated the influences of phosphorylation on the conformational ensembles and oligomerization dynamics of PHF6 by performing extensive all-atom molecular dynamics (MD) simulations. Our replica exchange MD simulations demonstrate that Y310 phosphorylation could effectively suppress the formation of β-structure and shift PHF6 oligomers toward coil-rich aggregates. The interaction analyses show that hydrogen bonding and hydrophobic interactions among PHF6 peptides, as well as Y310–Y310 π–π stacking and I308–Y310 CH−π interactions, are weakened by phosphorylation. Additional microsecond MD simulations show that Y310 phosphorylation could inhibit the oligomerization of PHF6 by preventing the formation of large β-sheet oligomers and multi-layer β-sheet aggregates. This study provides mechanistic insights into the phosphorylation-inhibited tau aggregation, which may be helpful for the in-depth understanding of the pathogenesis of tauopathies.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Atomistic Insights into the Inhibitory Mechanism of Tyrosine Phosphorylation against the Aggregation of Human Tau Fragment PHF6

et al. 2023

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“…475,477 SAXS studies 434 further indicated that the randomly oriented β-sheets of SRT are organized at the next hierarchical level into a hexagonally packed nanofibrillar lattice, as illustrated in Figure 10D-v. Using all atom discrete MD (DMD) simulations, Ding and co-workers 478,479 later confirmed the self-assembly of the [M1-M2] block copolymer architecture of suckerins, in particular corroborating that [M1] modules formed cross-β oligomers whereas [M2] modules exhibited a stronger self-assembly propensity but remained largely unstructured. These computational studies led the authors to propose a refined self-assembly model of suckerins driven by microphase separation between [M1] and [M2] modules, with [M2] acting as molecular glue and confining the β-sheet-rich [M1] modules into amyloid-like nano-assemblies.…”

Section: Gxxxxxxxdengxxxxxxfyxadgnxxxgfyxapxxxxxxmentioning

confidence: 87%

“…(i) The short peptide A1H1 can be self-assembled into stiff mesoscale fibers (left, reproduced with permission from ref . Copyright 2017 American Chemical Society) made of amyloid-like cross-β nanofibrils as predicted by MD simulations (right, reproduced from ref . Creative Commons CC BY-NC 4.0.…”

Section: Bioengineering Of Protein-based Materialsmentioning

confidence: 99%

Protein-Based Biological Materials: Molecular Design and Artificial Production

Miserez

Mohammadi

2023

Chem. Rev.

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Polymeric materials produced from fossil fuels have been intimately linked to the development of industrial activities in the 20th century and, consequently, to the transformation of our way of living. While this has brought many benefits, the fabrication and disposal of these materials is bringing enormous sustainable challenges. Thus, materials that are produced in a more sustainable fashion and whose degradation products are harmless to the environment are urgently needed. Natural biopolymerswhich can compete with and sometimes surpass the performance of synthetic polymersprovide a great source of inspiration. They are made of natural chemicals, under benign environmental conditions, and their degradation products are harmless. Before these materials can be synthetically replicated, it is essential to elucidate their chemical design and biofabrication. For protein-based materials, this means obtaining the complete sequences of the proteinaceous building blocks, a task that historically took decades of research. Thus, we start this review with a historical perspective on early efforts to obtain the primary sequences of load-bearing proteins, followed by the latest developments in sequencing and proteomic technologies that have greatly accelerated sequencing of extracellular proteins. Next, four main classes of protein materials are presented, namely fibrous materials, bioelastomers exhibiting high reversible deformability, hard bulk materials, and biological adhesives. In each class, we focus on the design at the primary and secondary structure levels and discuss their interplays with the mechanical response. We finally discuss earlier and the latest research to artificially produce protein-based materials using biotechnology and synthetic biology, including current developments by start-up companies to scale-up the production of proteinaceous materials in an economically viable manner.

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“…Furthermore, rigorous statistical mechanics theory can be applied to relate the ensemble of microscopic configurations with macroscopic thermodynamic properties. Classical molecular simulations have been applied to study a wide range of biomaterial systems such as supramolecular biopolymer, DNA-based bioconjugate, self-assembling peptides, − carbohydrate-based biomaterials, , and lipid membranes. − …”

Section: Methodsmentioning

confidence: 99%

Computational Design of Peptides for Biomaterials Applications

Wang

Stebe

Fuente-Núñez

et al. 2023

ACS Appl. Bio Mater.

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Computer-aided molecular design and protein engineering emerge as promising and active subjects in bioengineering and biotechnological applications. On one hand, due to the advancing computing power in the past decade, modeling toolkits and force fields have been put to use for accurate multiscale modeling of biomolecules including lipid, protein, carbohydrate, and nucleic acids. On the other hand, machine learning emerges as a revolutionary data analysis tool that promises to leverage physicochemical properties and structural information obtained from modeling in order to build quantitative protein structure−function relationships. We review recent computational works that utilize state-of-the-art computational methods to engineer peptides and proteins for various emerging biomedical, antimicrobial, and antifreeze applications. We also discuss challenges and possible future directions toward developing a roadmap for efficient biomolecular design and engineering.

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Molecular Insights into the Self‐Assembly of Block Copolymer Suckerin Polypeptides into Nanoconfined β‐Sheets

Cited by 13 publications

References 81 publications

Atomistic Insights into the Inhibitory Mechanism of Tyrosine Phosphorylation against the Aggregation of Human Tau Fragment PHF6

Atomistic Insights into the Inhibitory Mechanism of Tyrosine Phosphorylation against the Aggregation of Human Tau Fragment PHF6

Protein-Based Biological Materials: Molecular Design and Artificial Production

Computational Design of Peptides for Biomaterials Applications

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