Free energies and entropies of water molecules at the inhibitor-protein interface of DNA gyrase.
Complexes of the antibiotics novobiocin and clorobiocin with DNA gyrase are illustrative of the importance of bound water to binding thermodynamics. Mutants resistant to novobiocin as well as those with a decreased affinity for novobiocin over clorobiocin both involve a less favorable entropy of binding, which more than compensates for a more favorable enthalpy, and additional water molecules at the protein-ligand interface. Free energy, enthalpy, and entropy for these water molecules were calculated by thermodynamic integration computer simulations. The calculations show that addition of the water molecules is entropically unfavorable, with values that are comparable to the measured entropy differences. The free energies and entropies correlate with the change in the number of hydrogen bonds due to the addition of water molecules.
Department of Chemistry, University of New Orleans, New Orleans, Louisiana 70148, USA.
Hongtao
H
Yu
Steven W
SW
Rick
D000900:Anti-Bacterial Agents / Q000737:chemistry; D027081:DNA Gyrase / Q000737:chemistry* / Q000235:genetics; D019277:Entropy; D006860:Hydrogen Bonding; D050505:Mutant Proteins; D009675:Novobiocin / Q000031:analogs & derivatives / Q000737:chemistry; D013816:Thermodynamics; D059005:Topoisomerase II Inhibitors; D014867:Water / Q000737:chemistry*
D000900:Anti-Bacterial Agents; D050505:Mutant Proteins; D059005:Topoisomerase II Inhibitors; D014867:Water; D009675:Novobiocin; C006260:clorobiocin; D027081:DNA Gyrase