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Prediction of Aggregation of Biologically-Active Peptides with the UNRES Coarse-Grained Model

The UNited RESidue (UNRES) model of polypeptide chains was applied to study the association of 20 peptides with sizes ranging from 6 to 32 amino-acid residues. Twelve of those were potentially aggregating hexa- or heptapeptides excised from larger proteins, while the remaining eight contained potent...

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Autores principales: Biskupek, Iga, Czaplewski, Cezary, Sawicka, Justyna, Iłowska, Emilia, Dzierżyńska, Maria, Rodziewicz-Motowidło, Sylwia, Liwo, Adam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9406146/
https://www.ncbi.nlm.nih.gov/pubmed/36009034
http://dx.doi.org/10.3390/biom12081140
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author Biskupek, Iga
Czaplewski, Cezary
Sawicka, Justyna
Iłowska, Emilia
Dzierżyńska, Maria
Rodziewicz-Motowidło, Sylwia
Liwo, Adam
author_facet Biskupek, Iga
Czaplewski, Cezary
Sawicka, Justyna
Iłowska, Emilia
Dzierżyńska, Maria
Rodziewicz-Motowidło, Sylwia
Liwo, Adam
author_sort Biskupek, Iga
collection PubMed
description The UNited RESidue (UNRES) model of polypeptide chains was applied to study the association of 20 peptides with sizes ranging from 6 to 32 amino-acid residues. Twelve of those were potentially aggregating hexa- or heptapeptides excised from larger proteins, while the remaining eight contained potentially aggregating sequences, functionalized by attaching larger ends rich in charged residues. For 13 peptides, the experimental data of aggregation were used. The remaining seven were synthesized, and their properties were measured in this work. Multiplexed replica-exchange simulations of eight-chain systems were conducted at 12 temperatures from 260 to 370 K at concentrations from 0.421 to 5.78 mM, corresponding to the experimental conditions. The temperature profiles of the fractions of monomers and octamers showed a clear transition corresponding to aggregate dissociation. Low simulated transition temperatures were obtained for the peptides, which did not precipitate after incubation, as well as for the H-GNNQQNY-NH(2) prion–protein fragment, which forms small fibrils. A substantial amount of inter-strand β-sheets was found in most of the systems. The results suggest that UNRES simulations can be used to assess peptide aggregation except for glutamine- and asparagine-rich peptides, for which a revision of the UNRES sidechain–sidechain interaction potentials appears necessary.
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spelling pubmed-94061462022-08-26 Prediction of Aggregation of Biologically-Active Peptides with the UNRES Coarse-Grained Model Biskupek, Iga Czaplewski, Cezary Sawicka, Justyna Iłowska, Emilia Dzierżyńska, Maria Rodziewicz-Motowidło, Sylwia Liwo, Adam Biomolecules Article The UNited RESidue (UNRES) model of polypeptide chains was applied to study the association of 20 peptides with sizes ranging from 6 to 32 amino-acid residues. Twelve of those were potentially aggregating hexa- or heptapeptides excised from larger proteins, while the remaining eight contained potentially aggregating sequences, functionalized by attaching larger ends rich in charged residues. For 13 peptides, the experimental data of aggregation were used. The remaining seven were synthesized, and their properties were measured in this work. Multiplexed replica-exchange simulations of eight-chain systems were conducted at 12 temperatures from 260 to 370 K at concentrations from 0.421 to 5.78 mM, corresponding to the experimental conditions. The temperature profiles of the fractions of monomers and octamers showed a clear transition corresponding to aggregate dissociation. Low simulated transition temperatures were obtained for the peptides, which did not precipitate after incubation, as well as for the H-GNNQQNY-NH(2) prion–protein fragment, which forms small fibrils. A substantial amount of inter-strand β-sheets was found in most of the systems. The results suggest that UNRES simulations can be used to assess peptide aggregation except for glutamine- and asparagine-rich peptides, for which a revision of the UNRES sidechain–sidechain interaction potentials appears necessary. MDPI 2022-08-18 /pmc/articles/PMC9406146/ /pubmed/36009034 http://dx.doi.org/10.3390/biom12081140 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Biskupek, Iga
Czaplewski, Cezary
Sawicka, Justyna
Iłowska, Emilia
Dzierżyńska, Maria
Rodziewicz-Motowidło, Sylwia
Liwo, Adam
Prediction of Aggregation of Biologically-Active Peptides with the UNRES Coarse-Grained Model
title Prediction of Aggregation of Biologically-Active Peptides with the UNRES Coarse-Grained Model
title_full Prediction of Aggregation of Biologically-Active Peptides with the UNRES Coarse-Grained Model
title_fullStr Prediction of Aggregation of Biologically-Active Peptides with the UNRES Coarse-Grained Model
title_full_unstemmed Prediction of Aggregation of Biologically-Active Peptides with the UNRES Coarse-Grained Model
title_short Prediction of Aggregation of Biologically-Active Peptides with the UNRES Coarse-Grained Model
title_sort prediction of aggregation of biologically-active peptides with the unres coarse-grained model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9406146/
https://www.ncbi.nlm.nih.gov/pubmed/36009034
http://dx.doi.org/10.3390/biom12081140
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