Prediction of the three-dimensional structures of histone deacetylase 1 complexed with romidepsin and FK-A5

A. Oda, K. Kato, M. Morino, T. Nakayoshi, S. Fukuyoshi, K. Saijo, C. Ishioka, E. Kurimoto

Research output: Contribution to journalConference articlepeer-review

Abstract

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.

Original languageEnglish
Article number012019
JournalJournal of Physics: Conference Series
Volume1136
Issue number1
DOIs
Publication statusPublished - 2018 Dec 24
Event29th IUPAP Conference on Computational Physics, CCP 2017 - , France
Duration: 2017 Jul 92017 Jul 13

ASJC Scopus subject areas

  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'Prediction of the three-dimensional structures of histone deacetylase 1 complexed with romidepsin and FK-A5'. Together they form a unique fingerprint.

Cite this