Title : Molecular Docking and Dynamic Studies of Bioactive Compounds from Triticum aestivum(L.) Against Obesity Enzymes
Abstract:
Obesity is becoming a major health problem worldwide despite medical and political efforts to control its increased prevalence. Despite the recent success in identifying the molecular mechanisms controlling energy homoeostasis, the truth is that there are no efficient treatments besides surgical approaches. Thus an immediate challenge is to identify who among these obese individuals will be at high risk of developing metabolic complications. Overweight, obesity, and the metabolic syndrome have recently emerged as strong independent risk factors for CKD and ESRD.Today more than 1.1 billion people are overweight worldwide and 312 million are classified as obese. Adipogenesis is a process of adipocytes cell proliferation accompanied by adipocyte differentiation which is regulated by cascade involving many transcription factors PPARγ, C/EBPα and SREBP1c. Plants used for traditional medicine contain a wide range of substances to treat chronic as well as infectious diseases. Due to the development of adverse effects, microbial resistance to the chemically synthesized drugs, men turned to ethnopharmacognosy. They found literally thousands of phytochemicals from plants as safe-broadly effective alternatives with less adverse effect. The term “Alternative Medicine” became very common in western culture, focus on idea of using plants for medicinal purpose, as raw materials for extraction of active ingredients which used in the synthesis of different drugs. Triticum aestivum Linn. commonly called wheat grass under Gramineae, a genus of annual and biennial grasses. Wheat grass is a good source of mineral nutrients contains significant amounts of Fe, P, Mg, Mn, Cu and Zn also rich source of tocopherols with high vitamin E potency. It is also claimed to reduce hair graying, improves digestion, reduces high BP as it enhances the capillaries, support the growth of Lactobacilli, remove heavy metals from the body Obesity is caused primarily by lipid metabolism disorder. The enzymes involved in lipid metabolism used as targets in the development of new anti obesity drugs. Pancreatic lipase, key enzyme hydrolyzing 50−70% of total dietary fats. Therefore lipase inhibitors from plants considered as good source for anti obesity drugs. In addition, identifying such inhibitors will help to disclose the mechanisms of the plants nutritious effects. Study on the mechanism of molecular interaction between active compounds and enzymes can reveal pharmacokinetics as well as the relationship between the chemical structures and bioactivity of a drug. The molecular modeling study is another important tool for revealing the interactions between enzymes and their inhibitors, which could help to clarify directly the nature of binding between small molecules and enzymes. Molecular docking was used to explore the efficacy of Wg components to inhibit the key enzymes related with obesity.. The two important drug target protein/enzyme/receptor to study the quorum sensing mechanism using computational biology tools using Structure of human PTP1B catalytic domain and Structure of pancreatic lipase. Molecular dynamics studies revealed that Wg compounds had minimum potential energy with target protein. In order to understand the mechanism of ligand binding and to identify potent PTP 1B and PL inhibitors, a study involving molecular docking and virtual screening have been performed. It can be concluded that these phytochemicals or their derivatives can be used for further in-vitro and in- vivo studies to design valuable drugs.
