Comparison of QSAR and docking studies of histone deacetylase inhibitors

CHED 1289

Natasha R. Villanueva, dudleyn@william.jewell.edu and Jason A. Morrill. Department of Chemistry, William Jewell College, 500 College Hill, Liberty, MO 64068
Histone deacetylase inhibitors modulate transcriptional activity and promote apoptosis and differentiation within the cell. Because of this, HDAC inhibitors are being widely investigated as a proposed treatment of cancer. HDAC inhibitors function by binding to an enzyme's active site and inhibiting the deacetylation of lysine residues on target substrates. Using the program, AMPAC, structures of several HDAC inhibitors, including Trichostatin A and “proposed inhibitor” were built and optimized. These structures were then used to generate a QSAR model using the program, CODESSA, to predict biological activity. This model was then compared to previous docking studies used to predict binding energies, and literature values for model validation.