In Silico Identification of Novel Interactions for FABP5 (Fatty Acid-Binding Protein 5) with Nutraceuticals: Possible Repurposing Approach.

Abstract

Fatty Acid Binding-Protein 5 (FABP5) is a cytoplasmic protein, which binds long-chain fatty acids and other hydrophobic ligands. This protein is implicated in several physiological processes including mitochondrial β-oxidation and transport of fatty acids, membrane phospholipid synthesis, lipid metabolism, inflammation and pain. In the present study, we used molecular docking tools to determine the possible interaction of FABP5 with six selected compounds retrieved form Drugbank. Our results showed that FABP5 binding pocket included 31 polar and non-polar amino acids, and these residues may be related to phosphorylation, acetylation, ubiquitylation, and mono-methylation. Docking results showed that the most energetically favorable compounds are NADH (-9.12 kcal/mol), 5'-O-({[(Phosphonatooxy)phosphinato]oxy}phosphinato)adenosine (-8.62 kcal/mol), lutein (-8.25 kcal/mol), (2S)-2-[(4-{[(2-Amino-4-oxo-1,4,5,6,7,8-hexahydro-6-pteridinyl)methyl]amino}benzoyl)amino]pentanedioate (-7.17 kcal/mol), Pteroyl-L-glutamate (-6.86 kcal/mol) and (1S,3R,5E,7Z)-9,10-Secocholesta-5,7,10-triene-1,3,25-triol (-6.79 kcal/mol). Common interacting residues of FABP5 with nutraceuticals included SER16, LYS24, LYS34, LYS40 and LYS17. Further, we used the SwissADME server to determine the physicochemical and pharmacokinetic characteristics and to predict the ADME parameters of the selected nutraceuticals after molecular analysis by docking with the FABP5 protein. Amongst all compounds, pteroyl-L-glutamate is the only one meeting the Lipinski's rule of five criteria, demonstrating its potential pharmacological use. Finally, our results also suggest the importance of FABP5 in mediating the anti-inflammatory activity of the nutraceutical compounds.

• Authors: Ricardo Cabezas, Amirhossein Sahebkar, Valentina Echeverria, Janneth González Santos, Ghulam Md Ashraf, George E Barreto
• Journal: Advances in experimental medicine and biology (Adv Exp Med Biol) Vol. 1308 Pg. 589-599 ( 2021) ISSN: 0065-2598 [Print] United States
• PMID: 33861460 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Fatty Acid-Binding Proteins
• Ligands

Topics

• Anti-Inflammatory Agents
• Dietary Supplements
• Fatty Acid-Binding Proteins (genetics)
• Ligands
• Molecular Docking Simulation