  About half of human cancers show normal TP53 gene and aberrant overexpression
of Mdm2 and/or MdmX. This fact promotes a promising cancer therapeutic strategy
which targeting the interactions between p53 and Mdm2/MdmX. For developing the
inhibitors to disrupt the p53-Mdm2/MdmX interactions, we systematically
investigate structural and interaction characteristics of p53 and inhibitors
with Mdm2 and MdmX from atomistic level by exploiting stochastic molecular
dynamics simulations. We find that some specific $\alpha$ helices in Mdm2 and
MdmX structure play key role in their bindings with inhibitors and the hydrogen
bond formed by residue Trp23 of p53 with its counterpart in Mdm2/MdmX
determines dynamical competition processes of the disruption of Mdm2-p53
interaction and replacement of p53 from Mdm2-p53 complex {\it in vivo}. We hope
that the results reported in this paper provide basic information for designing
functional inhibitors and realizing cancer gene therapy.
