A comprehensive conformational analysis of bullacin B, a potent inhibitor of complex I. Molecular dynamics simulations and ab initio calculations.
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.
Bombasaro
José A
JA
Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, 5700 San Luis, Argentina.
Masman
Marcelo F
MF
Santágata
Luis N
LN
Freile
Mónica L
ML
Rodríguez
Ana M
AM
Enriz
Ricardo D
RD
D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D005663:Furans / Q000737:chemistry* / Q000494:pharmacology*; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D011789:Quantum Theory; D055672:Static Electricity; D013499:Surface Properties
D004791:Enzyme Inhibitors; D005663:Furans; D007783:Lactones; C532010:bullacin B; D042967:Electron Transport Complex I