Quantum mechanically derived AMBER-compatible heme parameters for various states of the cytochrome P450 catalytic cycle.

ABSTRACT: Molecular mechanics (MM) methods are computationally affordable tools for screening chemical libraries of novel compounds for sites of P450 metabolism. One challenge for MM methods has been the absence of a consistent and transferable set of parameters for the heme within the P450 active site. Experimental data indicate that mammalian P450 enzymes vary greatly in the size, architecture, and plasticity of their active sites. Thus, obtaining X-ray-based geometries for the development of accurate MM parameters for the major classes of hepatic P450 remains a daunting task. Our previous work with preliminary gas-phase quantum mechanics (QM)-derived atomic partial charges greatly improved the accuracy of docking studies of raloxifene to CYP3A4. We have therefore developed and tested a consistent

SUBMITTER: Shahrokh K 

PROVIDER: S-EPMC3242737 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature