title: Agonistic effect of polyunsaturated fatty acids (PUFAs) and its metabolites on brain-derived neurotrophic factor (BDNF) through molecular docking simulation.
abstract: BACKGROUND
  Brain-derived neurotrophic factor (BDNF) is a potent neurotrophic factor that is implicated in the regulation of food intake and body weight. Polyunsaturated fatty acids (PUFAs) localised in cell membranes have been shown to alter the levels of BDNF in the brain, suggesting that PUFAs and BDNF could have physical interaction with each other. To decipher the molecular mechanism through which PUFAs modulates BDNF's activity, molecular docking was performed for BDNF with PUFAs and its metabolites, with 4-Methyl Catechol as a control.
  
  
  RESULTS
  Inferring from molecular docking studies, lipoxin A4 (LXA4), and a known anti-inflammatory bioactive metabolite derived from PUFAs, with a binding energy of -3.98 Kcal/mol and dissociation constant of 1.2 mM showed highest binding affinity for BDNF in comparison to other PUFAs and metabolites considered in the study. Further, the residues Lys 18, Thr 20, Ala 21, Val 22, Phe 46, Glu 48, Lys 50, Lys 58, Thr 75, Gln 77, Arg 97 and Ile 98 form hot point motif, which on interaction enhances BDNF's function.
  
  
  CONCLUSIONS
  These results suggest that PUFAs and their metabolites especially, LXA4, modulate insulin resistance by establishing a physical interaction with BDNF. Similar interaction(s) was noted between BDNF and resolvins and protectins but were of lesser intensity compared to LXA4.
authors.affiliation: Department of Bioinformatics, Vision Research Foundation, Chennai 600006, India.
authors.forename: Umashankar
authors.initials: U
authors.lastname: Vetrivel
authors.forename: Sathya Baarathi
authors.initials: SB
authors.lastname: Ravichandran
authors.forename: Kaviarasan
authors.initials: K
authors.lastname: Kuppan
authors.forename: Jithu
authors.initials: J
authors.lastname: Mohanlal
authors.forename: Undurti Narasimha
authors.initials: UN
authors.lastname: Das
authors.forename: Angayarkanni
authors.initials: A
authors.lastname: Narayanasamy
mesh_terms: D020816:Amino Acid Motifs; D019208:Brain-Derived Neurotrophic Factor / Q000819:agonists / Q000737:chemistry*; D002396:Catechols / Q000737:chemistry; D005231:Fatty Acids, Unsaturated / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D011485:Protein Binding; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002396:Catechols; D005231:Fatty Acids, Unsaturated; C018599:4-methylcatechol