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Research Paper | Biology | India | Volume 3 Issue 6, June 2014
Functional Characterization and Structure Prediction of HDAC-10: A Bioinformatics Approach
Sabeena M | Kaiser Jamil [4]
Abstract: In eukaryotic cells; nuclear DNA is packaged around histone proteins. There are two enzymes namely Histone Acyl Transferases (HATs) and Histone Deacetylases (HDACs) that regulate the acetylation of histones and helps to condense the chromatin in its stable form. HDACs are considered as one of the promising targets in cancer biology studies. There are three major classes of mammalian HDACs which comprise of 18 genes. Since the crystal structure of HDAC-10 is not available yet; this molecular modeling study can be of great importance in structural biology especially in drug discovery researches. The aim of this study was to develop and validate model structure and the active site determination of HDAC-10 which is a class II member using Bioinformatics applications. The design of the model is based on a thorough evaluation of the HDAC-10 query sequence; Q969S8 by its primary sequence analysis using Expasy Protparam; Secondary analysis using Expasy SOPMA; Sequence similarity and alignment recognition using NCBI Protein BLAST; template alignment using LALIGN; and molecular modeling and dynamics studies using Swiss model and Deepview. Based on the individual sequence alignment scores obtained for query sequence; Q969S8 from LALIGN; four templates (3C0Y_A; 2VQO_A; 2VQJ_A and 2VQW_G) were selected for modeling. Each of these four templates was used for the modeling with the help of Swiss model and generated four corresponding models. The constructed models underwent minimization process in Deep View Swisspdb viewer. Validation protocols assessed the structure; fold and stereo chemical quality of the model. Rampage program showed model1 based on 3C0Y_A template and model 2 on 2VQO_A both were reliable but model 1 was considered as the best one; which showed 95.5 % residues in the most favorable region. Verify 3D acquired best value with 89.39 % of the residues had an average 3D-1D score of > 0.2 and Prosaweb recorded a Z score of -7.65. The predicted HDAC-10 model1 and its active site residues can be used for target based drug discovery process and it could be a promising receptor for docking and scoring studies.
Keywords: Template alignment, HDAC-10 model building and evaluation, Rampage program, active site prediction
Edition: Volume 3 Issue 6, June 2014,
Pages: 1792 - 1800