Molecular dynamics study of the binding of elsamicin A to DNA.
Molecular mechanics (MM) and dynamics (MD) were used to examine the conformational flexibility of elsamicin A, an antitumour antibiotic, in aqueous solution. Furthermore, MM and MD simulations were performed to obtain the first three-dimensional model of the elsamicin-A-DNA complex. Comparison of MD simulations of free and DNA-bound elsamicin A provided insight into the mechanism of DNA cleavage. Moreover, the drug-DNA complexes were analyzed to investigate specific drug-DNA interactions, as well as the role of the solvent water molecules in the drug-DNA binding. On the basis of the results derived from these simulations, several issues related to the sequence-selective binding of elsamicin A to DNA are discussed.
Alhambra
C
C
Departament de Farmàcia, Unitat Fisicoquímica, Facultat de Farmàcia, Universitat de Barcelona, Spain.
Luque
F J
FJ
Portugal
J
J
Orozco
M
M
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002240:Carbohydrate Sequence; D004247:DNA / Q000378:metabolism*; D004563:Electrochemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D004247:DNA; C049904:elsamicin A