Role of the fisetin on allergenic profilins: A theoretical approach

Introduction. The profilins are proteins of molecular weights between 12 to 15 kd that are found in all eukaryotic cells, it has been reported crossreactivity between species of homologous profilins. Polyphenols... [ view full abstract ]

Introduction. The profilins are proteins of molecular weights between 12 to 15 kd that are found in all eukaryotic cells, it has been reported crossreactivity between species of homologous profilins. Polyphenols have been the capacity to interfere with the allergic response, being able to bind to proteins in a reversible and irreversible ways. We found a polyphenol called fisetin with high bind at proteins.

Objective. The aim of present work was to evaluate the interactions between fisetin and allergic proteins like profilin, in search of binding to epitopes recognized by the immune system and result a cross reactions currently occurring with this type of proteins.

Method. We have used computational biology and chemistry, template-based modeling in the Modeller software, molecular dynamic (MD) simulations in the canonical ensemble, a simulation mode implemented in GROMACS. Graphic visualization in VMD, analysis of structural couplings by protein pocket’s prediction with ability to bind drug-like molecules with high affinity in PockDrug-Server and free-binding energy calculation with GROMACS.

Results and Discussion. Five profilins were studied: Ana c 1 (Ananas comosus), Cit s 2 (Citrus sinensis), Fra a 4 (Fragaria ananassa), Mal d 4 (Malus domestica) and Mus a 1 (Musa acuminata). The percent of homology been acceptable (>80%) in comparison to the template Art v 4 (Artemisa vulgaris). We have applied molecular dynamics simulations considering a canonical ensemble NVT (the number of particles N, the volume V, and the temperature T of the system are kept constant) by 100ns, in the OPLSAA force field using GROMACS. Molecular docking has a high score of druggability (0.9 - 1) and free-binding energy in the range of -62.31Kcal.mol^-1 to -57.81Kcal.mol^-1. We concluded that fisetin could be an effective ligand to block allergy reactions induced by profilins, an promising alternative in nanomedicine.