International Journal of Molecular Sciences

Journal Browser

► Journal Browser

Special Issue Information

Dear Colleagues,

Protein misfolding and the resulting oligomers and aggregates are implicated in various neurodegenerative diseases. At a molecular level, some of these species may be key neurotoxic agents. Experimental and computational analysis of these systems is an active field of great contemporary importance for ageing populations. This Special Issue will feature contributions from groups investigating misfolding at every level of detail, from initial misfolding to aggregation and the formation of larger amyloid aggregates. Original research articles and review papers elucidating how protein misfolding and the resulting oligomers and aggregates are implicated in various neurodegenerative diseases are very welcome from outstanding experts of the topic.

Dr. David J. Wales
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

protein misfolding
protein aggregation
genetic mutations
translational errors
abnormal protein modifications
incomplete complex formations

Published Papers (2 papers)

Download All Papers

Research

15 pages, 9091 KiB

Open AccessArticle

Transition Networks Unveil Disorder-to-Order Transformations in Aβ Caused by Glycosaminoglycans or Lipids

by Moritz Schäffler, Suman Samantray and Birgit Strodel

Int. J. Mol. Sci. 2023, 24(14), 11238; https://doi.org/10.3390/ijms241411238 - 8 Jul 2023

Cited by 4 | Viewed by 1081

Abstract

The aggregation of amyloid-

β

β

) peptides, particularly of A

β_{1 - 42}

, has been linked to the pathogenesis of Alzheimer’s disease. In this study, we focus on the conformational change of A

β_{1 - 42}

in the [...] Read more.

The aggregation of amyloid-

β

β

) peptides, particularly of A

β_{1 - 42}

, has been linked to the pathogenesis of Alzheimer’s disease. In this study, we focus on the conformational change of A

β_{1 - 42}

in the presence of glycosaminoglycans (GAGs) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipids using molecular dynamics simulations. We analyze the conformational changes that occur in A

β

by extracting the key structural features that are then used to generate transition networks. Using the same three features per network highlights the transitions from intrinsically disordered states ubiquitous in A

β_{1 - 42}

in solution to more compact states arising from stable

β

-hairpin formation when A

β_{1 - 42}

is in the vicinity of a GAG molecule, and even more compact states characterized by a

α

-helix or

β

-sheet structures when A

β_{1 - 42}

interacts with a POPC lipid cluster. We show that the molecular mechanisms underlying these transitions from disorder to order are different for the A

β_{1 - 42}

/GAG and A

β_{1 - 42}

/POPC systems. While in the latter the hydrophobicity provided by the lipid tails facilitates the folding of A

β_{1 - 42}

, in the case of GAG there are hardly any intermolecular A

β_{1 - 42}

–GAG interactions. Instead, GAG removes sodium ions from the peptide, allowing stronger electrostatic interactions within the peptide that stabilize a

β

-hairpin. Our results contribute to the growing knowledge of the role of GAGs and lipids in the conformational preferences of the A

β

peptide, which in turn influences its aggregation into toxic oligomers and amyloid fibrils. Full article

(This article belongs to the Special Issue Protein Misfolding)

► Show Figures

Figure 1

15 pages, 4493 KiB

Open AccessArticle

Energy Landscapes and Heat Capacity Signatures for Monomers and Dimers of Amyloid-Forming Hexapeptides

by Nicy and David J. Wales

Int. J. Mol. Sci. 2023, 24(13), 10613; https://doi.org/10.3390/ijms241310613 - 25 Jun 2023

Cited by 1 | Viewed by 777

Abstract

Amyloid formation is a hallmark of various neurodegenerative disorders. In this contribution, energy landscapes are explored for various hexapeptides that are known to form amyloids. Heat capacity (

C_{V}

) analysis at low temperature for these hexapeptides reveals that the low energy [...] Read more.

Amyloid formation is a hallmark of various neurodegenerative disorders. In this contribution, energy landscapes are explored for various hexapeptides that are known to form amyloids. Heat capacity (

C_{V}

) analysis at low temperature for these hexapeptides reveals that the low energy structures contributing to the first heat capacity feature above a threshold temperature exhibit a variety of backbone conformations for amyloid-forming monomers. The corresponding control sequences do not exhibit such structural polymorphism, as diagnosed via end-to-end distance and a dihedral angle defined for the monomer. A similar heat capacity analysis for dimer conformations obtained using basin-hopping global optimisation shows clear features in end-to-end distance versus dihedral correlation plots, where amyloid-forming sequences exhibit a preference for larger end-to-end distances and larger positive dihedrals. These results hold true for sequences taken from tau, amylin, insulin A chain, a de novo designed peptide, and various control sequences. While there is a little overall correlation between the aggregation propensity and the temperature at which the low-temperature

C_{V}

feature occurs, further analysis suggests that the amyloid-forming sequences exhibit the key

C_{V}

feature at a lower temperature compared to control sequences derived from the same protein. Full article

(This article belongs to the Special Issue Protein Misfolding)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Protein Misfolding

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (2 papers)

Research

Further Information

Guidelines

MDPI Initiatives

Follow MDPI