Molecular dynamic investigation of the interaction of supported affinity ligands with monoclonal antibodies

BIOT 158

Laura Zamolo, laura.zamolo@polimi.it, Valentina Busini, Davide Moiani, Davide Moscatelli, and Carlo Cavallotti. Dept. Chimica, Materiali e Ingegneria Chimica, G. Natta, Politecnico di Milano, Via Mancinelli, 7, Milano, Italy
Monoclonal antibodies are gaining an increasing importance in diagnostic and therapeutic treatment of acute diseases such as cancer. However, the production and purification of these pharmaceuticals is still extremely expensive. Among the different methods for MAB purification, affinity chromatography is one of the most employed, despite its cost. In this work we present our computational investigation aimed at obtaining some guidelines for the rational design of affinity ligands, through the study of their interactions with both the antibody (IgG) and a model support material (agarose). This analysis was carried out performing MD simulations of the support-spacer-ligand-IgG system in explicit water. Two commercial ligands and several spacers, which differ for hydrophobicity and chemical structure, were considered. Binding energies were determined with the LIE and MM-PBSA approaches. The results were compared with experimental data and revealed that the interaction of the ligand with spacer and support can significantly affect the binding process.