Protein environment affects the water-tryptophan binding mode. MD, QM/MM, and NMR studies of engrailed homeodomain mutants

Water molecules can interact with aromatic moieties using either their O-H bonds or their lone-pairs of electrons. In proteins, water-π interactions have been reported to occur with tryptophan and histidine residues, and dynamic exchange between O-Hπ hydrogen bonding and lone-pairπ interactions was...

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Veröffentlicht in:Physical chemistry chemical physics : PCCP Jg. 20; H. 18; S. 12664
Hauptverfasser: Špačková, Nad'a, Trošanová, Zuzana, Šebesta, Filip, Jansen, Séverine, Burda, Jaroslav V, Srb, Pavel, Zachrdla, Milan, Žídek, Lukáš, Kozelka, Jiří
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England 2018
Schlagworte:
Animals
Drosophila
Homeodomain Proteins - chemistry
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Magnetic Resonance Spectroscopy
Molecular Dynamics Simulation
Molecular Structure
Mutation
Protein Binding
Protein Domains
Quantum Theory
Transcription Factors - chemistry
Transcription Factors - genetics
Transcription Factors - metabolism
Tryptophan - chemistry
Tryptophan - metabolism
Water - chemistry
Water - metabolism
ISSN:1463-9084, 1463-9084
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Zusammenfassung:Water molecules can interact with aromatic moieties using either their O-H bonds or their lone-pairs of electrons. In proteins, water-π interactions have been reported to occur with tryptophan and histidine residues, and dynamic exchange between O-Hπ hydrogen bonding and lone-pairπ interactions was suggested to take place, based on ab initio calculations. Here we used classical and QM/MM molecular dynamics simulations, complemented with an NMR study, to examine a specific water-indole interaction observed in the engrailed homeodomain and in its mutants. Our simulations indicate that the binding mode between water and indole can adapt to the potential created by the surrounding amino acids (and by the residues at the DNA surface in protein-DNA complexes), and support the model of dynamic switching between the O-Hπ hydrogen bonding and lone-pairπ binding modes.
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ISSN:1463-9084
1463-9084
DOI:10.1039/c7cp08623g