Insight Into the Binding Mechanism of p53/pDIQ-MDMX/MDM2 With the Interaction Entropy Method.

ABSTRACT: The study of the p53-MDMX/MDM2 binding sites is a research hotspot for tumor drug design. The inhibition of p53-targeted MDMX/MDM2 has become an effective approach in anti-tumor drug development. In this paper, a theoretically rigorous and computationally accurate method, namely, the interaction entropy (IE) method, combined with the polarized protein-specific charge (PPC) force field, is used to explore the difference in the binding mechanism between p53-MDMX and p53-MDM2. The interaction of a 12mer peptide inhibitor (pDIQ), which is similar to p53 in structure, with MDMX/MDM2 is also studied. The results demonstrate that p53/pDIQ with MDM2 generates a stronger interaction than with MDMX. Compared to p53, pDIQ has larger binding free energies with MDMX and MDM2. According to the calculate

SUBMITTER: Li M 

PROVIDER: S-EPMC6361799 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature