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dc.contributor.author
Tang, Xuechen
dc.contributor.author
Kokot, Janik
dc.contributor.author
Waibl, Franz
dc.contributor.author
Fernández-Quintero, Monica L.
dc.contributor.author
Kamenik, Anna S.
dc.contributor.author
Liedl, Klaus R.
dc.date.accessioned
2023-12-07T15:24:28Z
dc.date.available
2023-12-06T07:58:35Z
dc.date.available
2023-12-07T15:24:28Z
dc.date.issued
2023-11-27
dc.identifier.issn
1549-9596
dc.identifier.issn
0095-2338
dc.identifier.issn
1520-5142
dc.identifier.other
10.1021/acs.jcim.3c01123
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/645837
dc.identifier.doi
10.3929/ethz-b-000645837
dc.description.abstract
We evaluated a workflow to reliably sample the conformational space of a set of 47 peptidic macrocycles. Starting from SMILES strings, we use accelerated molecular dynamics simulations to overcome high energy barriers, in particular, the cis-trans isomerization of peptide bonds. We find that our approach performs very well in polar solvents like water and dimethyl sulfoxide. Interestingly, the protonation state of a secondary amine in the ring only slightly influences the conformational ensembles of our test systems. For several of the macrocycles, determining the conformational distribution in chloroform turns out to be considerably more challenging. Especially, the choice of partial charges crucially influences the ensembles in chloroform. We address these challenges by modifying initial structures and the choice of partial charges. Our results suggest that special care has to be taken to understand the configurational distribution in apolar solvents, which is a key step toward a reliable prediction of membrane permeation of macrocycles and their chameleonic properties.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
American Chemical Society
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Addressing Challenges of Macrocyclic Conformational Sampling in Polar and Apolar Solvents: Lessons for Chameleonicity
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2023-11-09
ethz.journal.title
Journal of Chemical Information and Modeling
ethz.journal.volume
63
en_US
ethz.journal.issue
22
en_US
ethz.journal.abbreviated
J. Chem. Inf. Model.
ethz.pages.start
7107
en_US
ethz.pages.end
7123
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.status
published
en_US
ethz.date.deposited
2023-12-06T07:58:35Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2023-12-07T15:24:29Z
ethz.rosetta.lastUpdated
2024-02-03T07:55:02Z
ethz.rosetta.versionExported
true
ethz.COinS
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