| Title |
High-throughput virtual screening with e-pharmacophore and molecular simulations study in the designing of pancreatic lipase inhibitors
|
|---|---|
| Published in |
Drug Design, Development and Therapy, August 2015
|
| DOI | 10.2147/dddt.s84052 |
| Pubmed ID | |
| Authors |
Ganesh Kumar Veeramachaneni, K Kranthi Raj, Leela Madhuri Chalasani, Jayakumar Singh Bondili, Venkateswara Rao Talluri |
| Abstract |
Obesity is a progressive metabolic disorder in the current world population, and is characterized by the excess deposition of fat in the adipose tissue. Pancreatic lipase is one of the key enzymes in the hydrolysis of triglycerides into monoglycerides and free fatty acids, and is thus considered a promising target for the treatment of obesity. The present drugs used for treating obesity do not give satisfactory results, and on prolonged usage result in severe side effects. In view of the drastic increase in the obese population day-to-day, there is a greater need to discover new drugs with lesser side effects. High-throughput virtual screening combined with e-pharmacophore screening and ADME (absorption, distribution, metabolism, and excretion) and PAINS (pan-assay interference compounds) filters were applied to screen out the ligand molecules from the ZINC natural molecule database. The screened molecules were subjected to Glide XP docking to study the molecular interactions broadly. Further, molecular dynamic simulations were used to validate the stability of the enzyme-ligand complexes. Finally, the molecules with better results were optimized for in vitro testing. The screening protocols identified eight hits from the natural molecule database, which were further filtered through pharmacological filters. The final four hits were subjected to extra precision docking, and the complexes were finally studied with molecular dynamic simulations. The results pointed to the zinc 85893731 molecule as the most stable in the binding pocket, producing consistent H-bond interaction with Ser152 (G=-7.18). The optimized lead molecule exhibited good docking score, better fit, and improved ADME profile. The present study specifies zinc 85893731 as a lead molecule with higher binding score and energetically stable complex with pancreatic lipase. This lead molecule, along with its various analogs, can be further tested as a novel inhibitor against pancreatic lipase using in vitro protocols. |
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 72 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 72 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 14 | 19% |
| Student > Ph. D. Student | 12 | 17% |
| Student > Master | 9 | 13% |
| Researcher | 6 | 8% |
| Professor | 3 | 4% |
| Other | 10 | 14% |
| Unknown | 18 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 17 | 24% |
| Agricultural and Biological Sciences | 9 | 13% |
| Chemistry | 7 | 10% |
| Pharmacology, Toxicology and Pharmaceutical Science | 5 | 7% |
| Medicine and Dentistry | 3 | 4% |
| Other | 8 | 11% |
| Unknown | 23 | 32% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 April 2016.
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#20,655,488
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Outputs from Drug Design, Development and Therapy
#1,437
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Outputs of similar age from Drug Design, Development and Therapy
#100
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