期刊名称：International Journal of Computer Science Issues
印刷版ISSN：1694-0784
电子版ISSN：1694-0814
出版年度：2012
卷号：9
期号：2
出版社：IJCSI Press
摘要：Type 1 diabetes mellitus was formally known as IDDM, type I, or juvenile onset diabetes. Type 1 DM can occur at any age. In this study,we analyzed the involvement of HOX domain of PDX-1 protein.The homeodomain transcription factor, pancreas duodenum homeobox (PDX)-1, encoded by PDX-1 gene, which is a transcriptional activator of several genes, including insulin, somatostatin, glucokinase, islet amyloid polypeptide, and glucose transporter type 2 and essential for pancreas development, insulin production, and glucose homeostasis.[1,13]. HOX domain has a length of 63aa and control developmental patterns and cell differentiation in vertebrates by acting positive or negative regulators[4,9,16]. Different approached had been applied to identify the mutational hot spot region of HOX domain and calculate mutational frequency of the amino acids which resides in the hotspot region. Binding site of the domain had been identified and found that THR208, GLN246 ,VAL247, ASN253 involved in interaction with ligand. Potential Inhibitors had been screened on the basis of various criteria and bioactivity score had been calculated. Energy optimization was done by applying AMBER force field and steepest descent method. Docking was performed by CCDC GOLD, Molegro, HEX, and Argus lab to find the best potent inhibitor and increase the accuracy of the docking process. Sitagliptin showed satisfactory result on both docking and bioactivity analysis. It showed a GOLD fitness score of 49.8386 and had a moldock score of -122.919 with a ligand efficiency -4.33692. Compound had a bioactivity score of 0.56 for protease inhibitor. Sitagliptin showed good binding affinity to the target, which helps to work the pancreas in proper way and to secret insulin.
