Dynamic structure-based pharmacophore model development: a new and effective addition in the histone deacetylase 8 (HDAC8) inhibitor discovery.

ABSTRACT: Histone deacetylase 8 (HDAC8) is an enzyme involved in deacetylating the amino groups of terminal lysine residues, thereby repressing the transcription of various genes including tumor suppressor gene. The over expression of HDAC8 was observed in many cancers and thus inhibition of this enzyme has emerged as an efficient cancer therapeutic strategy. In an effort to facilitate the future discovery of HDAC8 inhibitors, we developed two pharmacophore models containing six and five pharmacophoric features, respectively, using the representative structures from two molecular dynamic (MD) simulations performed in Gromacs 4.0.5 package. Various analyses of trajectories obtained from MD simulations have displayed the changes upon inhibitor binding. Thus utilization of the dynamically-responded pro

SUBMITTER: Thangapandian S 

PROVIDER: S-EPMC3257139 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature