In silico comparison of interaction of allergen and human profilin 1 with natural ligands of human profilin 1

Abstract

IgE-mediated allergy, or type 1 hypersensitivity, is an acute reaction caused by allergen-induced cross-linking of IgE bound to FcεRs on the surface of effector cells. Birch pollen is a common cause of type 1 hypersensitivity affecting seasonal symptoms of allergic rhinitis and asthma-related emergencies. Bet v 1 (17 kDa) the immunodominant and most abundant allergenic protein in this pollen is a profilin. Profilins are proteins that regulate actin polymerization with functions that go beyond the cytoskeleton. Structural homology indicates that the G-actin-profilin interaction is conserved in all eukaryotic organisms with mechanistic differences in the binding of proline-rich ligands. Therefore, it is likely that exogenous profilins may play biological roles in humans. We tested this hypothesis with computational simulations to compare the predictable affinity of Bet v1 and human profilin 1 (Pf1H) for natural Pf1H ligands.

The structures obtained from the RSCB PDB of crystallized and digitalized samples (7mxl, 1pfl, 2pav, 4A87) were separated and the files re-edited to calculate the interaction energies (Kcal/mol) and their structural mean square deviations (RMSD-Angstroms) by means of USFC Chimera PyMol, Autodock Vina, Hdock and HADDOCK, software run on local I5 processors and on the EGI/EOSC high throughput computing (HTC) network employing 2 million processors in Europe.

The binding energies (Kcal/mol) of Bet v1 and Pf1H to VASP (Vasodilator-Stimulated phosphoprotein Peptide) were -7 and -6.4; with RMSD of 7 and 5; to monoclonal antibodies (IgG4) anti Bet v1 -25.2 and -27.3; with RMSD of 12.7 and 10.8 respectively. Binding energy values ​​describe higher affinity for the Bet-VASP pair than for Pf1H-VASP and higher affinity for the IgG4-Pf1H pair than IgG4-Bet. The RMSD of the complexes with VASP correspond to structures similar to the spontaneous ones and those of IgG4-Pf1H are more similar to the spontaneous ones than the IgG4-Bet, which would be the natural antigen.

These values, subject to experimental validation, allow us to hypothesize that exogenous profilins ​​could perform biological functions in addition to being allergens.