Publication details

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

Authors

ŠPAČKOVÁ Naděžda TROŠANOVÁ Zuzana SEBESTA F. JANSEN Séverine BURDA J.V. SRB Pavel ZACHRDLA Milan ŽÍDEK Lukáš KOZELKA Jiří

Type Article in Periodical
Magazine / Source Physical Chemistry Chemical Physics
MU Faculty or unit

Faculty of Science

Citation
Web https://pubs.rsc.org/en/Content/ArticleLanding/2018/CP/C7CP08623G#!divAbstract
Doi http://dx.doi.org/10.1039/c7cp08623g
Keywords NUCLEAR-MAGNETIC-RESONANCE; MOLECULAR-DYNAMICS; CRYSTAL-STRUCTURES; PROTON-EXCHANGE; DNA COMPLEX; CLEANEX-PM; SIMULATIONS; CONSTRAINTS; RESTRAINTS; PARAMETERS
Description Water molecules can interact with aromatic moieties using either their O-H bonds or their lone-pairs of electrons. In proteins, water-pi interactions have been reported to occur with tryptophan and histidine residues, and dynamic exchange between O-H center dot center dot center dot pi hydrogen bonding and lone-pair center dot center dot center dot pi 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-H center dot center dot center dot pi hydrogen bonding and lone-pair center dot center dot center dot pi binding modes.
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