Avaliação de representações oligoméricas para a modelagem in silico de polímeros molecularmente impressos utilizando molde de origem biológica

Abstract

Molecularly imprinted polymers (MIPs) are polymeric networks with significative relevance to analytical sensing, especially to biological processes. The molecular imprinting process allows the formation of functionalized and structurally complementary cavities to specific molecular templates, giving the material sensibility and specificity for instrumental analyses and, therefore, resulting in a wide variety of applications. However, the planning and development of MIPs is a slow and expensive process to be carried out entirely by experimental approaches, leading to computational tools being used to select some of the most critical parameters for imprinting, mainly ligand screening. Among all available methodologies, classical Molecular Dynamics is suitable to evaluate the imprinting process evolution and differentiate ligands according to their interaction with the target template. The most frequent modelling for functional ligands is the monomeric representation, however, this representation is unable to predict the interaction evolution as a function of polymer growth. In this context, this work aims to evaluate the influence of other oligomeric representations in the complexation phase of the P31 Asian-lineage Zika virus epitope through classical Molecular Dynamics. The functional ligands 2-vinylpyridine, 4-vinylaniline, acrylic acid, acrylamide and 2-hidroxyethylmethacrylate were simulated in mono-, tri- penta- and decameric chains, and were evaluated according to their influence on the epitope structural conservation and the ligand-template interactive profile. All systems were simulated in triplicates. Analyses of root-mean-square deviation (RMSD), radius of gyration (Rg), pair correlation function (g(r)), occupancy, average and maximum numbers of hydrogen-bonding type interaction showed the functional ligand chain size has an influence in the complexation phase. In terms of ligand screening, this influence emphasized and facilitated the differentiation between ligands. However, the behavior observed for larger chain sizes was only different from the monomeric chain in structural analyses, suggesting its use is best suited only when the template conformation exhibits high flexibility, such as in most biological templates.