Experimental and Computational Models for Side Chain Discrimination in Peptide–Protein Interactions
(2021) In Chemistry - A European Journal 27(42). p.10883-10897- Abstract
A bis(18-crown-6) Tröger's base receptor and 4-substituted hepta-1,7-diyl bisammonium salt ligands have been used as a model system to study the interactions between non-polar side chains of peptides and an aromatic cavity of a protein. NMR titrations and NOESY/ROESY NMR spectroscopy were used to analyze the discrimination of the ligands by the receptor based on the substituent of the ligand, both quantitatively (free binding energies) and qualitatively (conformations). The analysis showed that an all-anti conformation of the heptane chain was preferred for most of the ligands, both free and when bound to the receptor, and that for all of the receptor-ligand complexes, the substituent was located inside or partly inside of the aromatic... (More)
A bis(18-crown-6) Tröger's base receptor and 4-substituted hepta-1,7-diyl bisammonium salt ligands have been used as a model system to study the interactions between non-polar side chains of peptides and an aromatic cavity of a protein. NMR titrations and NOESY/ROESY NMR spectroscopy were used to analyze the discrimination of the ligands by the receptor based on the substituent of the ligand, both quantitatively (free binding energies) and qualitatively (conformations). The analysis showed that an all-anti conformation of the heptane chain was preferred for most of the ligands, both free and when bound to the receptor, and that for all of the receptor-ligand complexes, the substituent was located inside or partly inside of the aromatic cavity of the receptor. We estimated the free binding energy of a methyl- and a phenyl group to an aromatic cavity, via CH-π, and combined aromatic CH-π and π-π interactions to be −1.7 and −3.3 kJ mol−1, respectively. The experimental results were used to assess the accuracy of different computational methods, including molecular mechanics (MM) and density functional theory (DFT) methods, showing that MM was superior.
(Less)
- author
- Lidskog, Anna LU ; Dawaigher, Sami LU ; Solano Arribas, Carlos ; Ryberg, Anna ; Jensen, Jacob LU ; Bergquist, Karl Erik LU ; Sundin, Anders LU ; Norrby, Per Ola and Wärnmark, Kenneth LU
- organization
- publishing date
- 2021-07-26
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- computational chemistry, host–guest systems, NMR spectroscopy, NMR titrations, peptide-protein interactions
- in
- Chemistry - A European Journal
- volume
- 27
- issue
- 42
- pages
- 15 pages
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:33908678
- scopus:85108827518
- ISSN
- 0947-6539
- DOI
- 10.1002/chem.202100890
- language
- English
- LU publication?
- yes
- id
- 633c9427-8a4d-4cb3-afa3-1828a9a20d5a
- date added to LUP
- 2021-08-13 14:57:41
- date last changed
- 2024-04-20 09:18:08
@article{633c9427-8a4d-4cb3-afa3-1828a9a20d5a,
abstract = {{<p>A bis(18-crown-6) Tröger's base receptor and 4-substituted hepta-1,7-diyl bisammonium salt ligands have been used as a model system to study the interactions between non-polar side chains of peptides and an aromatic cavity of a protein. NMR titrations and NOESY/ROESY NMR spectroscopy were used to analyze the discrimination of the ligands by the receptor based on the substituent of the ligand, both quantitatively (free binding energies) and qualitatively (conformations). The analysis showed that an all-anti conformation of the heptane chain was preferred for most of the ligands, both free and when bound to the receptor, and that for all of the receptor-ligand complexes, the substituent was located inside or partly inside of the aromatic cavity of the receptor. We estimated the free binding energy of a methyl- and a phenyl group to an aromatic cavity, via CH-π, and combined aromatic CH-π and π-π interactions to be −1.7 and −3.3 kJ mol<sup>−1</sup>, respectively. The experimental results were used to assess the accuracy of different computational methods, including molecular mechanics (MM) and density functional theory (DFT) methods, showing that MM was superior.</p>}},
author = {{Lidskog, Anna and Dawaigher, Sami and Solano Arribas, Carlos and Ryberg, Anna and Jensen, Jacob and Bergquist, Karl Erik and Sundin, Anders and Norrby, Per Ola and Wärnmark, Kenneth}},
issn = {{0947-6539}},
keywords = {{computational chemistry; host–guest systems; NMR spectroscopy; NMR titrations; peptide-protein interactions}},
language = {{eng}},
month = {{07}},
number = {{42}},
pages = {{10883--10897}},
publisher = {{Wiley-Blackwell}},
series = {{Chemistry - A European Journal}},
title = {{Experimental and Computational Models for Side Chain Discrimination in Peptide–Protein Interactions}},
url = {{http://dx.doi.org/10.1002/chem.202100890}},
doi = {{10.1002/chem.202100890}},
volume = {{27}},
year = {{2021}},
}