The geometrical optimization of (3,3′)-diindolylmethane (DIM), an inhibitor of the bisubunit enzyme topoisomerase I from Leishmania donovani, a pathogenic protozoan parasite, mostly diffused in developing countries, has been carried out through quantum mechanical calculation. Using first-principle DFT restrained geometrical optimization, a potential energy surface has been constructed to identify a set of local minimum energy conformations of DIM. Starting from these conformations, the experimental UV−vis absorption spectrum in aqueous solution has been reproduced through TD-DFT calculations. A molecular mechanics classical force-field has been also parametrized and tested, verifying the correct coherence between the canonical ensemble obtained from molecular dynamics simulation and the potential energy surface calculation. The force field has been used to elucidate the interaction of DIM with a 22 bp DNA double strand. The best docked DIM-DNA complexes display a binding energy pretty similar to the experimental energy and are all located in the DNA minor groove, strongly suggesting that DIM is a minor groove binder.

Coletta, A., MOROZZO DELLA ROCCA, B., Jaisankar, P., Majumder, H., Chillemi, G., Sanna, N., et al. (2010). Assignment of UV-vis spectrum of (3,3')-diindolylmethane, a Leishmania donovani topoisomerase IB inhibitor and a candidate DNA minor groove binder, 114(26), 7121-7126 [10.1021/jp101494d].

Assignment of UV-vis spectrum of (3,3')-diindolylmethane, a Leishmania donovani topoisomerase IB inhibitor and a candidate DNA minor groove binder.

MOROZZO DELLA ROCCA, BLASCO;DESIDERI, ALESSANDRO
2010-01-01

Abstract

The geometrical optimization of (3,3′)-diindolylmethane (DIM), an inhibitor of the bisubunit enzyme topoisomerase I from Leishmania donovani, a pathogenic protozoan parasite, mostly diffused in developing countries, has been carried out through quantum mechanical calculation. Using first-principle DFT restrained geometrical optimization, a potential energy surface has been constructed to identify a set of local minimum energy conformations of DIM. Starting from these conformations, the experimental UV−vis absorption spectrum in aqueous solution has been reproduced through TD-DFT calculations. A molecular mechanics classical force-field has been also parametrized and tested, verifying the correct coherence between the canonical ensemble obtained from molecular dynamics simulation and the potential energy surface calculation. The force field has been used to elucidate the interaction of DIM with a 22 bp DNA double strand. The best docked DIM-DNA complexes display a binding energy pretty similar to the experimental energy and are all located in the DNA minor groove, strongly suggesting that DIM is a minor groove binder.
2010
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/11 - BIOLOGIA MOLECOLARE
English
Con Impact Factor ISI
Coletta, A., MOROZZO DELLA ROCCA, B., Jaisankar, P., Majumder, H., Chillemi, G., Sanna, N., et al. (2010). Assignment of UV-vis spectrum of (3,3')-diindolylmethane, a Leishmania donovani topoisomerase IB inhibitor and a candidate DNA minor groove binder, 114(26), 7121-7126 [10.1021/jp101494d].
Coletta, A; MOROZZO DELLA ROCCA, B; Jaisankar, P; Majumder, H; Chillemi, G; Sanna, N; Desideri, A
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/14118
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