Piperonyl butoxide-mediated inhibition of cytochrome P450-catalysed insecticide metabolism: a rational approach

The inhibitory effect of piperonyl butoxide (PBO) on cytochrome P450 was st udied by theoretical methods. Binding conformations of PBO were obtained by the recently developed low-mode conformational search within the active si te of cytochrome P450,,,. Increased activity of PBO relative to other methy lendioxyphenyl inhibitors was rationalized by its decreased conformational mobility and the steric block created by its long side-chain in the substra te access channel of the enzyme. (C) 1999 Society of Chemical Industry.