Dhananjay Kumar, Anshul Sarvate, Deblina Dey, Lakshmi Sahitya U, Kumar Gaurav Shankar, K. Kasturi / International Journal of Engineering Research and Applications (IJERA) ISSN: 2248-9622 www.ijera.com Vol. 3, Issue 1, January-February 2013, pp.023-033 23 | P a g e Molecular Modeling and Simulation Studies of Acyl CoA Synthetaseof Mycobacteriumleprae Dhananjay Kumar * , Anshul Sarvate 1 , Deblina Dey 1 , Lakshmi Sahitya U 2 , Kumar Gaurav Shankar 3 , K. Kasturi 2 *(Department of Bioinformatics, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Pune, Maharashtra 1(Department of Bioinformatics, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Pune, Maharashtra). 2(Department of Biotechnology, AcharyaNagarjuna University, Guntur, A. P.) 3(Department of Computer Science, JNU, India) ABSTRACT Leprosy or Hansen’s disease is caused by an obligate intracellular pathogen i.e. Mycobacterium leprae. Leprosy is a granulomatous disease of peripheral nerves and mucosa of the upper respiratory tract. This infectious disease results in Leprosy reactions that cause irreversible nerve damage and disabilities. The organism requires minimal set of functional genes for its survival. Most of the genes are involved in biosynthetic and metabolic pathways, so the product of these genes can be aimed for the novel drug target. Acyl CoA Synthetase is an enzyme that participates in fatty acid biosynthesis. The activation of fatty acids by Acyl-CoA Synthetase is the need of de novo lipid biosynthesis, fatty acid catabolism and remodeling of biological membranes. Therefore by emphasizing this protein as a drug target can help in the identification of novel drugs to cure leprosy. A well organized research comprising of analogue based drug design and molecular dynamics plays a major role in obtaining the lead molecules. The bacteria have developed resistance against many of the drugs available in the market. Therefore identification of the novel drug target and potent drug can be helpful in better prevention of the disease. Keywords- docking, homology modeling, leprosy, M.leprae, molecular, molecular dynamics, ramachandran plot. I Brief Introduction of Leprosy Leprosy was originated over 5000 years ago, almost going back to the Neolithic times 50 . Though remaining disfiguring strip conditions were perplexed with leprosy, deformities symptomatic of the disease now illustrious to be caused by Mycobacterium leprae are recognizable in umpteen archaeological finds 24 . One of the most famous example is the skull of Robert the Bruce that shows the artist symptom in systemic leprosy of nasal septum collapse. By gothic times, synchronous archeological relic shows that - at least in few societies - leprosy was diagnosed conservatively and thus mostly accurately 18 . Historically, the bulky numbers of bacterium in the tissues of lepromatous patients no doubtfulness led to the aetiologic agent. Thus, Mycobacteriumleprae, existence suggests that it is one of the first bacterium to be determined 24 .In 1873 first convincing association of a microorganism with a hominian disease, Armauer Hansen 27 , unconcealed the leprosy bacillus in skin biopsies but failed to culture Mycobacteriumleprae. A century afterwards the nine banded armadillo 33 , was victimized as a replacement host enabling huge quantities of the bacillus which has been kept apart for biochemical and physiological studies 59 . Consequent efforts to corroborate procreation in synthetic media acquired have been equally futile, although metabolic activity can be sensed 21 . Leprosy is one of the oldest filmed diseases, relic a serious health problem though prevalence has been low extensively by 1947, as dapsone (4, 4¢- diaminodiphenylsulphone) was discovered. At that time it became the only effective, but exclusive weakly bactericidal, anti-leprosy drug. The figure of cases of leprosy worldwide remained at roughly 11 million finished to the early-1980s but by then, dapsone resistant strains of M. leprae had enlarged to appraising levels. The imperative comeback by the World Health Organization to this problem was to acquire multi-drug regimens against M. leprae. Since the treatment now included apace antiseptic medicine, rifampicin and also the treatment had good coverage, so the number of cases as expected drops down 71 . At one stage dominance of leprosy was around 3 million, though incidence (i.e. rate of appearance of new cases) remains as high as before multi-drug therapy was introduced 53 and immunization with BCG 34,47 , the incidence of disease remains bedevilment with more than 690,000 new person reported annnualy 72 . The most main usage in the leprosy check in the penultimate millennium has been the launching of multi-drug therapy (MDT) 54 in 1982; recommendation of the WHO study group 10 . Freely visible long-term multi- drug therapy that combines rifampicin, clofazimine