Home > Publications database > Different Force Fields Give Rise to Different Amyloid Aggregation Pathways in Molecular Dynamics Simulations > print

001     889721
005     20210215175046.0
024 7 _ |a 10.1021/acs.jcim.0c01063
|2 doi
024 7 _ |a 0095-2338
|2 ISSN
024 7 _ |a 1520-5142
|2 ISSN
024 7 _ |a (BIS
|2 ISSN
024 7 _ |a 44.2004)
|2 ISSN
024 7 _ |a 1549-9596
|2 ISSN
024 7 _ |a 1549-960X
|2 ISSN
024 7 _ |a 2128/26808
|2 Handle
024 7 _ |a altmetric:94161142
|2 altmetric
024 7 _ |a 33174726
|2 pmid
024 7 _ |a WOS:000608875100080
|2 WOS
037 _ _ |a FZJ-2021-00343
082 _ _ |a 540
100 1 _ |a Samantray, Suman
|0 P:(DE-Juel1)176383
|b 0
|u fzj
245 _ _ |a Different Force Fields Give Rise to Different Amyloid Aggregation Pathways in Molecular Dynamics Simulations
260 _ _ |a Washington, DC
|c 2020
|b American Chemical Society64160
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1610983410_8202
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a The progress toward understanding the molecularbasis of Alzheimers’s disease is strongly connected to elucidatingthe early aggregation events of the amyloid-β (Aβ) peptide.Molecular dynamics (MD) simulations provide a viable techniqueto study the aggregation of Aβ into oligomers with high spatial andtemporal resolution. However, the results of an MD simulation canonly be as good as the underlying force field. A recent study by ourgroup showed that none of the common force fields can distinguishbetween aggregation-prone and nonaggregating peptide sequences, producing a similar and in most cases too fast aggregationkinetics for all peptides. Since then, new force fields specially designed for intrinsically disordered proteins such as Aβ weredeveloped. Here, we assess the applicability of these new force fields to studying peptide aggregation using the Aβ16−22 peptide andmutations of it as test case. We investigate their performance in modeling the monomeric state, the aggregation into oligomers, andthe stability of the aggregation end product, i.e., the fibrillar state. A main finding is that changing the force field has a stronger effecton the simulated aggregation pathway than changing the peptide sequence. Also the new force fields are not able to reproduce theexperimental aggregation propensity order of the peptides. Dissecting the various energy contributions shows that AMBER99SB-dispoverestimates the interactions between the peptides and water, thereby inhibiting peptide aggregation. More promising results areobtained with CHARMM36m and especially its version with increased protein−water interactions. It is thus recommended to usethis force field for peptide aggregation simulations and base future reparameterizations on it.
536 _ _ |a 553 - Physical Basis of Diseases (POF3-553)
|0 G:(DE-HGF)POF3-553
|c POF3-553
|f POF III
|x 0
588 _ _ |a Dataset connected to CrossRef
700 1 _ |a Yin, Feng
|0 P:(DE-Juel1)176537
|b 1
|u fzj
700 1 _ |a Kav, Batuhan
|0 P:(DE-Juel1)178946
|b 2
|u fzj
700 1 _ |a Strodel, Birgit
|0 P:(DE-Juel1)132024
|b 3
|e Corresponding author
773 _ _ |a 10.1021/acs.jcim.0c01063
|g Vol. 60, no. 12, p. 6462 - 6475
|0 PERI:(DE-600)1491237-5
|n 12
|p 6462 - 6475
|t Journal of chemical information and modeling
|v 60
|y 2020
|x 1549-960X
856 4 _ |u https://juser.fz-juelich.de/record/889721/files/acs.jcim.0c01063.pdf
856 4 _ |y Published on 2020-11-11. Available in OpenAccess from 2021-11-11.
|u https://juser.fz-juelich.de/record/889721/files/2020.09.09.290320v1.full.pdf
909 C O |o oai:juser.fz-juelich.de:889721
|p openaire
|p open_access
|p VDB
|p driver
|p dnbdelivery
910 1 _ |a Forschungszentrum Jülich
|0 I:(DE-588b)5008462-8
|k FZJ
|b 0
|6 P:(DE-Juel1)176383
910 1 _ |a Forschungszentrum Jülich
|0 I:(DE-588b)5008462-8
|k FZJ
|b 1
|6 P:(DE-Juel1)176537
910 1 _ |a Forschungszentrum Jülich
|0 I:(DE-588b)5008462-8
|k FZJ
|b 2
|6 P:(DE-Juel1)178946
910 1 _ |a Forschungszentrum Jülich
|0 I:(DE-588b)5008462-8
|k FZJ
|b 3
|6 P:(DE-Juel1)132024
913 1 _ |a DE-HGF
|b Key Technologies
|l BioSoft – Fundamentals for future Technologies in the fields of Soft Matter and Life Sciences
|1 G:(DE-HGF)POF3-550
|0 G:(DE-HGF)POF3-553
|3 G:(DE-HGF)POF3
|2 G:(DE-HGF)POF3-500
|4 G:(DE-HGF)POF
|v Physical Basis of Diseases
|x 0
914 1 _ |y 2020
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
|d 2020-08-28
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
|d 2020-08-28
915 _ _ |a Embargoed OpenAccess
|0 StatID:(DE-HGF)0530
|2 StatID
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b J CHEM INF MODEL : 2018
|d 2020-08-28
915 _ _ |a WoS
|0 StatID:(DE-HGF)0113
|2 StatID
|b Science Citation Index Expanded
|d 2020-08-28
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
|d 2020-08-28
915 _ _ |a IF < 5
|0 StatID:(DE-HGF)9900
|2 StatID
|d 2020-08-28
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1150
|2 StatID
|b Current Contents - Physical, Chemical and Earth Sciences
|d 2020-08-28
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0160
|2 StatID
|b Essential Science Indicators
|d 2020-08-28
915 _ _ |a Nationallizenz
|0 StatID:(DE-HGF)0420
|2 StatID
|d 2020-08-28
|w ger
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
|d 2020-08-28
920 _ _ |l yes
920 1 _ |0 I:(DE-Juel1)IBI-7-20200312
|k IBI-7
|l Strukturbiochemie
|x 0
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a UNRESTRICTED
980 _ _ |a I:(DE-Juel1)IBI-7-20200312
980 1 _ |a FullTexts

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21