In-silico screening of potential inhibitors of HMGCoA reductase and Lanosterol synthase, key enzymes in cholesterol biosynthesis pathway

Chandra, N Sai Venkata Sarath (2014) In-silico screening of potential inhibitors of HMGCoA reductase and Lanosterol synthase, key enzymes in cholesterol biosynthesis pathway. BTech thesis.



Hyperlipidemia is elevated level of lipids or lipoproteins in our body. Cholesterol is a major lipid particle circulating in our body. Cholesterol synthesis takes place in liver and this biosynthesis pathway is called Mevalonate pathway. Cholesterol is the end product of this Mevalonate pathway. Several enzymes play a role in the Cholesterol biosynthesis. Enzymes like HMGCoA synthase, HMGCoA reductase, Farnesyl PP synthase, Lanosterol synthase, Squalene synthase. This cholesterol is mainly responsible for several health effects especially Coronary heart diseases, atherosclerosis etc. So now in order to prevent the cholesterol synthesis in our body, we need to find potent inhibitors against the above enzymes and there after modify them as drugs. In this study, two enzymes HMGCoA reductase and Lanosterol synthase were targeted. For our docking study, we used Arguslab, Mgl tools, Autodock vina softwares for obtaining binding energies of protein and ligands. We search for already available drugs acting against HMGCoA reductase called Statins. We obtained binding energy results with NADH, PRAVASTATIN, LOVASTATIN, CERIVASTATIN, SIMVASTATIN, FLUVASTATIN, BEZAFIBRATE and note them as POSITIVE CONTROL 1. Then we dock HMGCoA reductase with natural molecules and compare them with positive control 1. In the next step, we targeted Lanosterol Synthase with available Quinuclidine inhibitors and results obtained was noted as POSITIVE CONTROL 2. Now we cross docked Lanosterol synthase with previous natural ligands and compared them with Positive control 2. We later found the toxicity and druglikeness of all inhibitors used against both the targets. We found two natural molecules APIGENIN and NARINGENIN which showed best binding energy results against both the targets. Both Apigenin and Naringenin act as suitable inhibitors against HMGCoA reductase and Lanosterol synthase inhibiting at two places along the Mevalonate pathway.

Item Type:Thesis (BTech)
Uncontrolled Keywords:Hyperlipidemia; cholesterol; HMGCoA reductase; Lanosterol synthase; Statins; Apigenin; Naringenin
Subjects:Engineering and Technology > Biomedical Engineering
Divisions: Engineering and Technology > Department of Biotechnology and Medical Engineering
ID Code:6420
Deposited By:Hemanta Biswal
Deposited On:11 Sep 2014 14:53
Last Modified:11 Sep 2014 14:53
Supervisor(s):Sarkar, N

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