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Experimental and Computational Models for Side Chain Discrimination in Peptide–Protein Interactions
- Source :
- Chemistry (Weinheim an Der Bergstrasse, Germany)
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
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 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.<br />A model system to study interactions between aromatic cavities and non‐polar side chains was developed and studied by different NMR methods, where a weak but evident side‐chain discrimination was observed. The experimental quantitative and qualitative data was used to evaluate different computational methods, with the conclusion that for this system, molecular mechanics gave more accurate results than density functional theory calculations.
- Subjects :
- Magnetic Resonance Spectroscopy
Molecular Conformation
Substituent
Hot Paper
Molecular Dynamics Simulation
Ligands
010402 general chemistry
01 natural sciences
Catalysis
chemistry.chemical_compound
NMR spectroscopy
Side chain
Phenyl group
Host–guest chemistry
Full Paper
010405 organic chemistry
Ligand
host–guest systems
Organic Chemistry
NMR titrations
General Chemistry
Nuclear magnetic resonance spectroscopy
Full Papers
computational chemistry
peptide-protein interactions
0104 chemical sciences
Crystallography
chemistry
Density functional theory
Peptides
Two-dimensional nuclear magnetic resonance spectroscopy
Subjects
Details
- ISSN :
- 15213765 and 09476539
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Chemistry – A European Journal
- Accession number :
- edsair.doi.dedup.....2f60f11efc24683945fc760b9312f423