Agonistic effect of polyunsaturated fatty acids (PUFAs) and its metabolites on brain-derived neurotrophic factor (BDNF) through molecular docking simulation

Umashankar Vetrivel,Sathya Baarathi Ravichandran,Angayarkanni Narayanasamy,Jithu Mohanlal,Kaviarasan Kuppan,Undurti Narasimha Das

doi:10.1186/1476-511x-11-109

Abstract

BackgroundBrain-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.ResultsInferring 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 1.2mM 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.ConclusionThese 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.

Highlights

Neurotrophins protect and promote the growth and development of nerves [1]
It is interesting to note that Brain-derived neurotrophic factor (BDNF) and TrkB are expressed in the retinal ganglion cell layer and are able to influences the morphological differentiation of the cells and act as cell survival factors [22,23]. Since both BDNF and n-3 Polyunsaturated fatty acids (PUFAs) levels are known to be altered in diabetes and several other neurological conditions, our current study aims to investigate the effect of PUFAs and their metabolites on BDNF binding towards the receptor, tropomyosin-related kinase-B (TrkB) and its function through molecular docking simulation
Molecular Dynamics simulation of BDNF MD simulation of the monomeric form of BDNF was analyzed to gain a better insight into the stability and dynamics nature of the molecule

Summary

Introduction

Neurotrophins protect and promote the growth and development of nerves [1] They have potent effects on neuronal differentiation, survival, neurite outgrowth, synaptic formation, and plasticity [2,3]. BDNF plays a crucial role in controlling body weight and energy homeostasis [5]. Increased levels of BDNF reduce food consumption and maintain energy balance [6]. Both central and peripheral administration of BDNF decreased food intake, increased energy expenditure and ameliorated hyperinsulinaemia and hyperglycaemia in diabetic db/db mice [7,8,9,10]. Brain-derived neurotrophic factor (BDNF) is a potent neurotrophic factor that is implicated in the regulation of food intake and body weight. 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

Methods

Results

Conclusion