http://www.cnr.it/ontology/cnr/individuo/prodotto/ID4050
Dissociation of minor groove binders from DNA: insights from metadynamics simulations (Articolo in rivista)
- Type
- Label
- Dissociation of minor groove binders from DNA: insights from metadynamics simulations (Articolo in rivista) (literal)
- Anno
- 2008-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.1093/nar/gkn561 (literal)
- Alternative label
Vargiu, AV; Ruggerone, P; Magistrato, A; Carloni, P (2008)
Dissociation of minor groove binders from DNA: insights from metadynamics simulations
in Nucleic acids research
(literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Vargiu, AV; Ruggerone, P; Magistrato, A; Carloni, P (literal)
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- Rivista
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- Note
- ISI Web of Science (WOS) (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
- \"[Vargiu, Attilio Vittorio; Ruggerone, Paolo] Univ Cagliari, CNR, INFM, SLACS, I-09042 Cagliari, Italy; [Vargiu, Attilio Vittorio; Ruggerone, Paolo] Univ Cagliari, Dept Phys, I-09042 Cagliari, Italy; [Magistrato, Alessandra; Carloni, Paolo] CNR INFM DEMOCRITOS, I-34014 Trieste, Italy; [Magistrato, Alessandra; Carloni, Paolo] SISSA, ISAS, I-34014 Trieste, Italy (literal)
- Titolo
- Dissociation of minor groove binders from DNA: insights from metadynamics simulations (literal)
- Abstract
- We have used metadynamics to investigate the mechanism of noncovalent dissociation from DNA by two representatives of alkylating and noncovalent minor groove (MG) binders. The compounds are anthramycin in its anhydrous form (IMI) and distamycin A (DST), which differ in mode of binding, size, flexibility and net charge. This choice enables to evaluate the influence of such factors on the mechanism of dissociation. Dissociation of IMI requires an activation free energy of similar to 12 kcal/mol and occurs via local widening of the MG and loss of contacts between the drug and one DNA strand, along with the insertion of waters in between. The detachment of DST occurs at a larger free energy cost, similar to 16.5 or similar to 18 kcal/mol depending on the binding mode. These values compare well with that of 16.6 kcal/mol extracted from stopped-flow experiments. In contrast to IMI, an intermediate is found in which the ligand is anchored to the DNA through its amidinium tail. From this conformation, binding and unbinding occur almost at the same rate. Comparison between DST and with kinetic models for the dissociation of Hoechst 33258 from DNA uncovers common characteristics across different classes of noncovalent MG ligands. (literal)
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