10.6084/m9.figshare.9611324.v1 Leandro A. Alves Avelar Leandro A. Alves Avelar Dusan Ruzic Dusan Ruzic Nemanja Djokovic Nemanja Djokovic Thomas Kurz Thomas Kurz Katarina Nikolic Katarina Nikolic Structure-based design of selective histone deacetylase 6 zinc binding groups Taylor & Francis Group 2019 Histone deacetylase fragment-based drug design molecular docking epigenetics zinc binding group 2019-08-14 11:02:38 Journal contribution https://tandf.figshare.com/articles/journal_contribution/Structure-based_design_of_selective_histone_deacetylase_6_zinc_binding_groups/9611324 <p>The binding site of the second catalytic domain of human histone deacetylase 6 (HDAC6 CDII) has structural features that differ from the other human orthologues, being also mainly responsible for the overall enzymatic activity of this isoform. Aiming to identify new fragments as a possible novel selective zinc binding group (ZBG) for HDAC6 CDII, two fragment libraries were designed: one library consisting of known chelators and a second one using the fragments of the ZINC15 database. The most promising fragments identified in a structure-based virtual screening of designed libraries were further evaluated through molecular docking and molecular dynamics simulations. An interesting benzimidazole fragment was selected from the <i>in silico</i> studies and presented as potential zing binding group for the development of novel HDAC6 selective inhibitors.</p> <p>Communicated by Ramaswamy H. Sarma</p>