International Journal of Computational Bioinformatics and In Silico Modeling
ABSTRACT: This article has been REMOVED from Aizeon Publishers database with effective from 25 May 2014, at the request of the corresponding author, Atalay Mesfin Anteneh.
REASON for WITHDRAWL: The author intends to enhance the study design parameters.
ABSTRACT: Structural analysis of the multidrug resistance-associated protein 1 (MRP1) nucleotide-binding domain 1 (NBD1) model and a docking simulation between 6-(methylsulfinyl)hexyl isothiocyanate (6MITC) and the NBD1 model were performed with a software package the Molecular Operating Environment (MOE). An NBD1 (PDB code: 2CBZ) of human MRP1 was selected for the 3D structure modeling of the NBD1 model. The Site Finder module of the MOE identified 11 possible ligand-binding sites in the modeled NBD1. The docking simulation revealed that 6MITC possibly inhibits functions of NBD1 interferring with Val680, Lys684, Ser685, Gln713, Gln714, Asp792, Asp793, Thr826 and His827. To the best of our knowledge, this is the first report of an NBD1 model with 6MITC, and our data verify that the 6MITC-NBD1 model can be utilized for application to target MRP1 for the development of anticancer drugs.
KeyWords: 6-(Methylsulfinyl)hexyl isothiocyanate (6MITC), ATP-binding cassette (ABC) transporters, in silico, multidrug resistance-associated protein 1 (MRP1), nucleotide-binding domain 1 (NBD1)
How to cite: Hideaki Yamaguchi et al. Int J Comput Bioinfo In Silico Model. 3(1) 2014: 310-314
ABSTRACT: The glycoside hydrolase family 8 (GH-8) consists of bifunctional cellulase-chitosanases many of which are produced by species of Bacillus. Chitosanolytic enzymes can be useful in producing low molecular weight chitooligosaccharides which have several applications. In addition, a bifunctional enzyme would be more beneficial than the use of two individual enzymes in the production of chitooligosaccharides and in the degradation of the complex cellulose, chitin and chitosan rich biomass that occurs in nature. The crystal structure of a previously determined GH-8 chitosanase has revealed that the catalytic site is constructed on a scaffold of a double α6/α6 barrel which consists of six helix-loop-helix motifs. Bifunctional cellulase-chitosanases from Bacillus species isolated hitherto were analysed and were found to have the double α6/α6 barrel as previously predicted. The signature pattern of glycoside hydrolase family 8 (GH-8) was determined for the sequences. Some of the protein sequences among them were modelled and their closest structural analogs were determined. The structures were found to be related to endoglucanases, xylanases, epimerases and also terpenoid cyclases all of which have the double α6/α6 barrel architecture. This study provides a detailed insight into the structure of cellulase-chitosanase catalytic core and identifies related enzymes with similar catalytic core thereby signifying a possible evolutionary relationship.
KeyWords: Glycoside hydrolase family 8; Bacillus; six hairpin glycosidases; chitosanase-cellulases; homology modelling
How to cite: Niveditha Prakash and Shubha Gopal. Int J Comput Bioinfo In Silico Model. 3(1) 2013: 315-320
ABSTRACT: This paper deals with the way that Ibn al-Haytham used qiyas (inference and induction by analogy) as an experimental research method in the natural sciences. The paper introduces and analyzes the tools of the analogical method of research, the extent of their application to natural phenomena and discusses an example, taken from the history of the natural sciences that involve analogical qiyas methodology: Ibn al-Haytham's method of research in optics. Qiyas was known in Islamic culture as a method of research in the religious juristic sciences, but it was used also in the natural sciences. This movement in itself can be considered an important turn in the history of science, as it constituted a change of the method of research in these sciences, from deduction, which had been prevalent for centuries, to qiyas (type of analogical reasoning). The application of this novel method of research in natural sciences at that time contributed a lot to the development of the modern sciences.
KeyWords: analogical reasoning, qiyas, Ibn al-Haytham, induction, Research philosophy, Research methodology
How to cite: Sobhi Rayan. Int J Comput Bioinfo In Silico Model. 3(1) 2013: 321-326
ABSTRACT: Cholesteryl esterase is the key enzyme involved in the hydrolysis of lipids and transport of free cholesterol. The hydrolysis of dietary cholesterol ester into cholesterol by cholesteryl esterase in the intestinal lumen is an essential process for its absorption. The reduction of cholesterol absorption by inhibiting cholesteryl esterase is a new target site of intervention for the treatment of hyperlipidaemia. Currently, Statin drugs are prescribed to decrease the serum low density lipid levels, but they have been found to cause many adverse side effects. The above situation necessitated the need to develop suitable phytotherapeutic agents with less frequent side effects. It is expected that phytomedicines developed from indigenous cardiotonic medicinal plant scan offer new dimensions for the management of hyperlipidemia and associated cardiac problems. Terminalia cuneata Roth (syn. Terminalia arjuna Wight & Arn; Family: Combretaceae), is a promising cardiotonic medicinal plant, having wider applications in indigenous systems of medicine. The present study involved molecular docking of pancreatic cholesteryl esterase (1F6W) and 28 phytochemicals reported from Terminalia cuneata Roth. using an automated docking software AutoDock 4.2, GOLD Suite of Programs 5.2 and iGEMDOCK. The 3D structure of cholesteryl esterase (PDB ID: IF6W) and the ligand molecules were retrieved from protein databank, PDB and chemical database, PubChem of NCBI respectively. The 3D structure of phytochemicals that were not available in any databases, were drawn and created using ChemSketch and an online 3D generation tool CORINA respectively. Dempster-Shafer theory (DST) is used to select the high top ranking compounds from different docking tools. Of the 28 molecules, five of them showed best ligand binding energy which are Ellagic acid, Gallic acid, Leucocyanidin, Luteolin and Pyrocatechol. The autodock results were also compared with the GOLD and iGEMDOCK results. By using Dempster-Shafer theory (DST), luteolin identified as best lead compound from the plant T. cuneata. We believe that the luteolin compound from the plant T. cuneata has the potential to regulate the cholesterol level in the blood by limiting the activity of the enzyme, pancreatic cholesteryl esterase.
KeyWords: Terminalia cuneata, cholesteryl esterase, Autodock, GOLD, iGEMDOCK
How to cite: Rini Abraham et. al. Int J Comput Bioinfo In Silico Model. 3(1) 2013: 327-331