In Silico Evaluation of Oligomeric Representations for Molecularly Imprinted Polymer Modeling Using a Biological Template

• Published in: Journal of chemical information and modeling Vol. 63; no. 21; pp. 6740 - 6755
• Main Authors: Oliveira Soté, William, de Araújo Rodrigues, Aurélia Aparecida, Comar Junior, Moacyr
• Format: Journal Article
• Language: English
• Published: Washington American Chemical Society 13.11.2023
• Subjects: Acrylamide; Acrylic acid; Biological activity; Complex formation; Computational Chemistry; Correlation; Hydrogen bonding; Imprinted polymers; Ligands; Molecular dynamics; Monomers; Representations; Software; Trimers
• ISSN: 1549-9596; 1549-960X; 1549-960X
• DOI: 10.1021/acs.jcim.3c01461

Molecularly imprinted polymers (MIPs) have significant relevance to analytical sensing due to their functionalized and template-specific structurally complementary cavities, providing increased sensibility and specificity for instrumental analyses, thereby enabling a wide variety of applications, especially for biological processes. Designing and developing MIPs entirely by experimental approaches are time-consuming and costly processes; thus, computational tools are used to assess some of the most critical parameters for imprinting, such as ligand screening. A typical practice is to model functional ligands as monomers; however, this representation fails to predict how ligand–template interactions evolve during polymer growth. In this context, this work aims to evaluate whether additional oligomeric representations affect the formation of noncovalent complexes between typical ligands and the P31 Asian lineage Zika virus epitope, using classical molecular dynamics. The ligands 2-vinylpyridine, 4-vinylaniline, acrylic acid, acrylamide, and 2-hidroxyethyl methacrylate were simulated as monomers, trimers, pentamers, and decamers, and their influence on the epitope structural conservation and ligand–template interactions were evaluated. Analyses of root-mean-square deviation, fluctuation, radius of gyration, pair correlation function, and number of hydrogen bonding-type interactions were conducted, showing the ligand chain size had an influence on the complex formation. However, this influence had no discernible pattern, exhibiting better performance in some cases while noninfluential in others. Of particular significance, in terms of epitope structural conservation, distinct oligomeric chains led to the selection of the distinct most interactive ligands. This observation raises important questions regarding the use of oligomeric chains in MIP simulations, thus prompting the need for further investigations of this subject.