Protein environment affects the water–tryptophan binding mode. MD, QM/MM, and NMR studies of engrailed homeodomain mutants
| Autor: | Filip Šebesta, Séverine Jansen, Jaroslav V. Burda, Milan Zachrdla, Nad'a Špačková, Jiří Kozelka, Pavel Srb, Zuzana Trošanová, Lukáš Žídek |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Magnetic Resonance Spectroscopy Stereochemistry General Physics and Astronomy Molecular Dynamics Simulation 010402 general chemistry 01 natural sciences QM/MM 03 medical and health sciences Molecular dynamics Protein Domains Animals Drosophila Proteins Molecule Physical and Theoretical Chemistry Histidine Homeodomain Proteins Molecular Structure Hydrogen bond Chemistry Tryptophan Water Nuclear magnetic resonance spectroscopy engrailed 0104 chemical sciences 030104 developmental biology Mutation Quantum Theory Drosophila Protein Binding Transcription Factors |
| Zdroj: | Physical Chemistry Chemical Physics. 20:12664-12677 |
| ISSN: | 1463-9084 1463-9076 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|