The role of entropy in initializing the aggregation of peptides: a first principle study on oligopeptide oligomerization

Autores
Pohl, Gábor; Jákli, Imre; Csizmadia, Imre G.; Papp, Dóra; Garibotto, Francisco Matías; Perczel, András
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The initiation and progression of Alzheimer's disease is coupled to the oligo- and polymerization of amyloid peptides in the brain. Amyloid like aggregates of protein domains were found practically independent of their primary sequences. Thus, the driving force of the transformation from the original to a disordered amyloid fold is expected to lie in the protein backbone common to all proteins. In order to investigate the thermodynamics of oligomerization, full geometry optimizations and frequency calculations were performed both on parallel and antiparallel β-pleated sheet model structures of [HCO–(Ala)1–6–NH2]2 and (For–Ala1–2–NH2)1–6peptides, both at the B3LYP and M05-2X/6-311++G(d,p)//M05-2X/6-31G(d) levels of theory, both in vacuum and in water. Our results show that relative entropy and enthalpy both show a hyperbolic decrease with increasing residue number and with increasing number of strands as well. Thus, di- and oligomerization are always thermodynamically favored. Antiparallel arrangements were found to have greater stability than parallel arrangements of the polypeptide backbones. During our study the relative changes in thermodynamic functions are found to be constant for long enough peptides, indicating that stability and entropy terms are predictable. All thermodynamic functions of antiparallel di- and oligomers show a staggered nature along the increasing residue number. By identifying and analyzing the 6 newly emerging dimer vibrational modes of the 10- and 14-membered building units, the staggered nature of the entropy function can be rationalized. Thus, the vanishing rotational and translational modes with respect to single strands are converted into entropy terms “holding tight” the dimers and oligomers formed, rationalizing the intrinsic adherence of natural polypeptide backbones to aggregate.
Fil: Pohl, Gábor. Eötvös Loránd University; Hungría
Fil: Jákli, Imre. Eötvös Loránd University; Hungría
Fil: Csizmadia, Imre G.. Eötvös Loránd University; Hungría
Fil: Papp, Dóra. Eötvös Loránd University; Hungría
Fil: Garibotto, Francisco Matías. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina
Fil: Perczel, András. Eötvös Loránd University; Hungría
Materia
Alzheimers Disease
Polymerization of Amyloid Peptides
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/14506

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spelling The role of entropy in initializing the aggregation of peptides: a first principle study on oligopeptide oligomerizationPohl, GáborJákli, ImreCsizmadia, Imre G.Papp, DóraGaribotto, Francisco MatíasPerczel, AndrásAlzheimers DiseasePolymerization of Amyloid Peptideshttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1The initiation and progression of Alzheimer's disease is coupled to the oligo- and polymerization of amyloid peptides in the brain. Amyloid like aggregates of protein domains were found practically independent of their primary sequences. Thus, the driving force of the transformation from the original to a disordered amyloid fold is expected to lie in the protein backbone common to all proteins. In order to investigate the thermodynamics of oligomerization, full geometry optimizations and frequency calculations were performed both on parallel and antiparallel β-pleated sheet model structures of [HCO–(Ala)1–6–NH2]2 and (For–Ala1–2–NH2)1–6peptides, both at the B3LYP and M05-2X/6-311++G(d,p)//M05-2X/6-31G(d) levels of theory, both in vacuum and in water. Our results show that relative entropy and enthalpy both show a hyperbolic decrease with increasing residue number and with increasing number of strands as well. Thus, di- and oligomerization are always thermodynamically favored. Antiparallel arrangements were found to have greater stability than parallel arrangements of the polypeptide backbones. During our study the relative changes in thermodynamic functions are found to be constant for long enough peptides, indicating that stability and entropy terms are predictable. All thermodynamic functions of antiparallel di- and oligomers show a staggered nature along the increasing residue number. By identifying and analyzing the 6 newly emerging dimer vibrational modes of the 10- and 14-membered building units, the staggered nature of the entropy function can be rationalized. Thus, the vanishing rotational and translational modes with respect to single strands are converted into entropy terms “holding tight” the dimers and oligomers formed, rationalizing the intrinsic adherence of natural polypeptide backbones to aggregate.Fil: Pohl, Gábor. Eötvös Loránd University; HungríaFil: Jákli, Imre. Eötvös Loránd University; HungríaFil: Csizmadia, Imre G.. Eötvös Loránd University; HungríaFil: Papp, Dóra. Eötvös Loránd University; HungríaFil: Garibotto, Francisco Matías. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaFil: Perczel, András. Eötvös Loránd University; HungríaRoyal Society of Chemistry2012-01-28info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/14506Pohl, Gábor; Jákli, Imre; Csizmadia, Imre G.; Papp, Dóra; Garibotto, Francisco Matías; et al.; The role of entropy in initializing the aggregation of peptides: a first principle study on oligopeptide oligomerization; Royal Society of Chemistry; Physical Chemistry Chemical Physics; 14; 4; 28-1-2012; 1507-15161463-9076enginfo:eu-repo/semantics/altIdentifier/url/http://pubs.rsc.org/en/Content/ArticleLanding/2012/CP/C2CP22821A#!divAbstractinfo:eu-repo/semantics/altIdentifier/doi/ 10.1039/c2cp22821ainfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:44:32Zoai:ri.conicet.gov.ar:11336/14506instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:44:33.289CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The role of entropy in initializing the aggregation of peptides: a first principle study on oligopeptide oligomerization
title The role of entropy in initializing the aggregation of peptides: a first principle study on oligopeptide oligomerization
spellingShingle The role of entropy in initializing the aggregation of peptides: a first principle study on oligopeptide oligomerization
Pohl, Gábor
Alzheimers Disease
Polymerization of Amyloid Peptides
title_short The role of entropy in initializing the aggregation of peptides: a first principle study on oligopeptide oligomerization
title_full The role of entropy in initializing the aggregation of peptides: a first principle study on oligopeptide oligomerization
title_fullStr The role of entropy in initializing the aggregation of peptides: a first principle study on oligopeptide oligomerization
title_full_unstemmed The role of entropy in initializing the aggregation of peptides: a first principle study on oligopeptide oligomerization
title_sort The role of entropy in initializing the aggregation of peptides: a first principle study on oligopeptide oligomerization
dc.creator.none.fl_str_mv Pohl, Gábor
Jákli, Imre
Csizmadia, Imre G.
Papp, Dóra
Garibotto, Francisco Matías
Perczel, András
author Pohl, Gábor
author_facet Pohl, Gábor
Jákli, Imre
Csizmadia, Imre G.
Papp, Dóra
Garibotto, Francisco Matías
Perczel, András
author_role author
author2 Jákli, Imre
Csizmadia, Imre G.
Papp, Dóra
Garibotto, Francisco Matías
Perczel, András
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Alzheimers Disease
Polymerization of Amyloid Peptides
topic Alzheimers Disease
Polymerization of Amyloid Peptides
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The initiation and progression of Alzheimer's disease is coupled to the oligo- and polymerization of amyloid peptides in the brain. Amyloid like aggregates of protein domains were found practically independent of their primary sequences. Thus, the driving force of the transformation from the original to a disordered amyloid fold is expected to lie in the protein backbone common to all proteins. In order to investigate the thermodynamics of oligomerization, full geometry optimizations and frequency calculations were performed both on parallel and antiparallel β-pleated sheet model structures of [HCO–(Ala)1–6–NH2]2 and (For–Ala1–2–NH2)1–6peptides, both at the B3LYP and M05-2X/6-311++G(d,p)//M05-2X/6-31G(d) levels of theory, both in vacuum and in water. Our results show that relative entropy and enthalpy both show a hyperbolic decrease with increasing residue number and with increasing number of strands as well. Thus, di- and oligomerization are always thermodynamically favored. Antiparallel arrangements were found to have greater stability than parallel arrangements of the polypeptide backbones. During our study the relative changes in thermodynamic functions are found to be constant for long enough peptides, indicating that stability and entropy terms are predictable. All thermodynamic functions of antiparallel di- and oligomers show a staggered nature along the increasing residue number. By identifying and analyzing the 6 newly emerging dimer vibrational modes of the 10- and 14-membered building units, the staggered nature of the entropy function can be rationalized. Thus, the vanishing rotational and translational modes with respect to single strands are converted into entropy terms “holding tight” the dimers and oligomers formed, rationalizing the intrinsic adherence of natural polypeptide backbones to aggregate.
Fil: Pohl, Gábor. Eötvös Loránd University; Hungría
Fil: Jákli, Imre. Eötvös Loránd University; Hungría
Fil: Csizmadia, Imre G.. Eötvös Loránd University; Hungría
Fil: Papp, Dóra. Eötvös Loránd University; Hungría
Fil: Garibotto, Francisco Matías. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina
Fil: Perczel, András. Eötvös Loránd University; Hungría
description The initiation and progression of Alzheimer's disease is coupled to the oligo- and polymerization of amyloid peptides in the brain. Amyloid like aggregates of protein domains were found practically independent of their primary sequences. Thus, the driving force of the transformation from the original to a disordered amyloid fold is expected to lie in the protein backbone common to all proteins. In order to investigate the thermodynamics of oligomerization, full geometry optimizations and frequency calculations were performed both on parallel and antiparallel β-pleated sheet model structures of [HCO–(Ala)1–6–NH2]2 and (For–Ala1–2–NH2)1–6peptides, both at the B3LYP and M05-2X/6-311++G(d,p)//M05-2X/6-31G(d) levels of theory, both in vacuum and in water. Our results show that relative entropy and enthalpy both show a hyperbolic decrease with increasing residue number and with increasing number of strands as well. Thus, di- and oligomerization are always thermodynamically favored. Antiparallel arrangements were found to have greater stability than parallel arrangements of the polypeptide backbones. During our study the relative changes in thermodynamic functions are found to be constant for long enough peptides, indicating that stability and entropy terms are predictable. All thermodynamic functions of antiparallel di- and oligomers show a staggered nature along the increasing residue number. By identifying and analyzing the 6 newly emerging dimer vibrational modes of the 10- and 14-membered building units, the staggered nature of the entropy function can be rationalized. Thus, the vanishing rotational and translational modes with respect to single strands are converted into entropy terms “holding tight” the dimers and oligomers formed, rationalizing the intrinsic adherence of natural polypeptide backbones to aggregate.
publishDate 2012
dc.date.none.fl_str_mv 2012-01-28
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/14506
Pohl, Gábor; Jákli, Imre; Csizmadia, Imre G.; Papp, Dóra; Garibotto, Francisco Matías; et al.; The role of entropy in initializing the aggregation of peptides: a first principle study on oligopeptide oligomerization; Royal Society of Chemistry; Physical Chemistry Chemical Physics; 14; 4; 28-1-2012; 1507-1516
1463-9076
url http://hdl.handle.net/11336/14506
identifier_str_mv Pohl, Gábor; Jákli, Imre; Csizmadia, Imre G.; Papp, Dóra; Garibotto, Francisco Matías; et al.; The role of entropy in initializing the aggregation of peptides: a first principle study on oligopeptide oligomerization; Royal Society of Chemistry; Physical Chemistry Chemical Physics; 14; 4; 28-1-2012; 1507-1516
1463-9076
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://pubs.rsc.org/en/Content/ArticleLanding/2012/CP/C2CP22821A#!divAbstract
info:eu-repo/semantics/altIdentifier/doi/ 10.1039/c2cp22821a
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Royal Society of Chemistry
publisher.none.fl_str_mv Royal Society of Chemistry
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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