| Title |
Probing the intermolecular interactions of PPARγ-LBD with polyunsaturated fatty acids and their anti-inflammatory metabolites to infer most potential binding moieties
|
|---|---|
| Published in |
Lipids in Health and Disease, January 2017
|
| DOI | 10.1186/s12944-016-0404-3 |
| Pubmed ID | |
| Authors |
Shalini Muralikumar, Umashankar Vetrivel, Angayarkanni Narayanasamy, Undurti N. Das |
| Abstract |
PPARγ is an isoform of peroxisome proliferator-activated receptor (PPAR) belonging to a super family of nuclear receptors. PPARγ receptor is found to play a crucial role in the modulation of lipid and glucose homeostasis. Its commotion has been reported to play a significant role in a broad spectrum of diseases such as type 2 diabetes mellitus, inflammatory diseases, Alzheimer's disease, and in some cancers. Hence, PPARγ is an important therapeutic target. Polyunsaturated fatty acids (PUFAs) and their metabolites (henceforth referred to as bioactive lipids) are known to function as agonists of PPARγ. However, agonistic binding modes and affinity of these ligands to PPARγ are yet to be deciphered. In this study, we performed a comparative molecular docking, binding free energy calculation and molecular dynamics simulation to infer and rank bioactive lipids based on the binding affinities with the ligand binding domain (LBD) of PPARγ. The results inferred affinity in the order of resolvin E1 > neuroprotectin D1 > hydroxy-linoleic acid > docosahexaenoic acid > lipoxin A4 > gamma-linolenic acid, arachidonic acid > alpha-linolenic acid > eicosapentaenoic acid > linoleic acid. Of all the bioactive lipids studied, resolvin E1, neuroprotectin D1 and hydroxy-linoleic acid showed significant affinity comparable to proven PPARγ agonist namely, rosiglitazone, in terms of Glide XP docking score, H-bond formation with the key residues, binding free energy and stable complex formation with LBD favouring co-activator binding, as inferred through Molecular Dynamics trajectory analysis. Hence, these three bioactive lipids (resolvin E1, neuroprotectin D1 and hydroxy-linoleic acid) may be favourably considered as ideal drug candidates in therapeutic modulation of clinical conditions such as type 2 DM, Alzheimer's disease and other instances where PPARγ is a key player. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
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 61 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Japan | 1 | 2% |
| Unknown | 60 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 12 | 20% |
| Researcher | 12 | 20% |
| Student > Ph. D. Student | 6 | 10% |
| Professor > Associate Professor | 4 | 7% |
| Student > Doctoral Student | 3 | 5% |
| Other | 6 | 10% |
| Unknown | 18 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 9 | 15% |
| Agricultural and Biological Sciences | 7 | 11% |
| Biochemistry, Genetics and Molecular Biology | 6 | 10% |
| Pharmacology, Toxicology and Pharmaceutical Science | 6 | 10% |
| Nursing and Health Professions | 4 | 7% |
| Other | 11 | 18% |
| Unknown | 18 | 30% |
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 23 January 2017.
All research outputs
#18,525,776
of 22,947,506 outputs
Outputs from Lipids in Health and Disease
#986
of 1,451 outputs
Outputs of similar age
#308,984
of 418,332 outputs
Outputs of similar age from Lipids in Health and Disease
#18
of 31 outputs
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