COMPUTATIONAL MODELLING AND FUNCTIONAL CHARACTERIZATION OF HDAC-11

In eukaryotes, DNA is packaged into chromatin structures, whose basic unit is the nucleosome. A principle component of chromatin that plays an important role in the regulation of DNA is the modification of histones. Since histones are post-translationally modified, there inludes a large number of different histone post-translational modifications. These histone modifications create a repressive environment for gene expression, which in case of histone acetylation, are controlled by competing activities of two families of enzymes, histone acetyltransferases (HAT’s) and histone deacetylases (HDACs). HDAC11 is a class IV protein of the HDAC family.  The present aim of this study is to develop a model of HDAC11 by using bioinformatics applications. The design of the model is based on thorough evaluation of the HDAC-11 query sequence, Q96DB2, which was retrieved from UniProtKB. The physiochemical and primary analysis were computed using ExPASy Protparam tool. Functional characterization was computed using RaptorX, HMMTOP and Softberry Server’s CYS_REC tool (Cysteine Recognition Server) which predicted the secondary structure composition, presence of transmembrane proteins and the presence of cysteine residues respectively. The molecular model was generated using PHYRE2 server, since it was best suited as it provided higher query sequence coverage and confidence. Model refinement was computed using UCSF Chimera V1.9 and validation was performed using RAMPAGE server which explains the feature of Psi and Phi angle orientation. Verify 3D Structure Evaluation Server was used to determine the 3D-profiling of the residues in the model. The overall quality score of the model was calculated by ProSA Web Server