A comprehensive conformational analysis of bullacin B, a potent inhibitor of complex I. Molecular dynamics simulations and ab initio calculations.

Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, 5700 San Luis, Argentina.

Using a conformational systematic search combined with semiempirical and ab initio (RHF/3-21G and RHF/6-31G(d)) calculations, the conformational space of bullacin B was examined for the first time. In addition, molecular dynamics simulations were carried out to better evaluate the conformational behavior of this acetogenin. Our results indicate that bullacin B possesses a significant molecular flexibility. Although many different conformations were identified, at ab initio level, the L forms were energetically mostly preferred. Our results support the use of molecular dynamics simulations for this compound suggesting that a combined decane/water system is a good solvent system to simulate the biological environment of this molecule acting as inhibitor of complex I.

PMID: 18651725 [PubMed - indexed for MEDLINE]