Romidepsin is an anticancer drug that inhibits histone deacetylase (HDAC) in human cells. Recently, we found that romidepsin and its analog, FK-A5, inhibit phosphoinositide 3-kinase. Thus, romidepsin and FK-A5 are expected to be promising HDAC/PI3K dual inhibitors for anticancer therapy. In this study, the HDAC1-inhibitor complex structures were predicted by using computational docking and molecular dynamics (MD) simulations. Because romidepsin and FK-A5 are large cyclic molecules, large numbers of conformers can be obtained for these molecules by computational chemical treatment. The docking poses were extracted by comparing romidepsin and FK-A5 because similar compounds are recognized by proteins in similar binding modes. MD simulations were conducted for the selected docking poses, and the protein-ligand interactions were analyzed. The computational results are expected to be useful for the rational drug design of HDAC inhibitors.
|Journal of Physics: Conference Series
|Published - 2018 Dec 24
|29th IUPAP Conference on Computational Physics, CCP 2017 - , France
Duration: 2017 Jul 9 → 2017 Jul 13