  Histone deacetylase (HDAC) and Histone acetyl-transferase (HAT) are enzymes
that influence transcription by selectively deacetylating or acetylating the
(epsilon)-amino groups of lysine located near the amino termini of core histone
proteins. Over expression of HDACs noted in many forms of cancers including
leukemia and breast cancer. HDAC inhibitors have been shown to be potent
inducers of growth arrest, differentiation, and/or apoptotic cell death. There
is a growing interest in the development of histone deacetylase inhibitors as
anti cancer agents. Three known ligands of HDAC-8 were taken and docked. The
best scores were analyzed and structures similar to these ligands were
downloaded using carol and corina databases and docked. Also large databases of
small molecules were computationally screened using molecular docking for hits
that can conformationally and chemically fit to the active site. Molecules
which got high scores for both GoldScore and ChemScore were selected and
compared with the previous results. Those with best results were then taken for
calculating H-bond interactions and close contacts. Bioactivity prediction of
the best ranked ligands was done. Their physicochemical properties were also
analyzed. Four new molecules were identified and suggested for further testing
in the wet lab.
