Computational modeling of Soluplus® nanomicelles and IgG interactions: a potential approach for targeting Shiga toxin type 2 and prevent Hemolytic Uremic Syndrome

CASAL JUAN JOSÉ; GIRÓN REYES CLAUDIO DANIEL; AMARAL, MARIA MARTA; SACERDOTI FLAVIA

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAB AAFE AACYTAL 2023; 2023

SAIC SAB AAFE AACYTAL

Shiga toxin type 2 (Stx2) is secreted by Shiga toxin producingEscherichia coli during infection and is responsible for developingHemolytic Uremic Syndrome (HUS), a systemic disease characterizedby hemolytic anemia, thrombocytopenia and acute kidneyinjury. Nowadays, there is no specific treatment available for HUS.Soluplus® is an amphiphilic polymer that spontaneously assemblesin nanomicelles (NM) in aqueous solutions and is commonly usedfor solubilization and administration of poorly soluble drugs. We proposethat Soluplus® nanomicelles associated with anti Stx2 IgG mayimprove IgG properties of toxin neutralization and propose them asa treatment for HUS. In this study we aimed to investigate potentialinteractions between Soluplus® and IgG by computational modelingto better understand the association between both molecules. Forthat, the crystal structure of Soluplus® was designed using MarvinChemsketch 23.10, based on information from the manufacturer.A reduced version of Soluplus® was generated, preserving themonomer proportions and resulting in a molecule with a molecularweight of 42 kDa. Docking calculations were performed using AutoDockVina 1.2.5 with the IgG antibody (PDB code 1IGY) as themodel protein. The search box, centered on amino acid GLY236 ofthe B chain, had dimensions of 126 Å in each direction (x, y, z).The docking results were analyzed based on the scoring function,which implicitly incorporated the solvent effect. The pose with thelowest binding energy was selected for further analysis. Interactionsbetween Soluplus® and the IgG antibody were examined using Lig-Plot+ 2.2.8. Our computational modeling indicates that Soluplus®interacts with IgG mostly by the Fc portion of the antibody, thus suggestingthat IgG may perform a corona in the nanomicelles and givea better solubilization of the IgG in aqueous solutions. These resultsare in concordance with the biological studies that indicate that NMimprove the neutralization capacity of anti Stx2 IgG in vitro, suggestingthat coupling IgG to Soluplus® could be a potential strategy to prevent HUS.