A Study on the Effect of an Aptamer with an Embedded Phosphate-Methylated Nucleotide on the Binding of a Target Molecule Using Molecular Simulation

Uncharged DNA analogues are frequently used to be synthesized as oligomers or combined with nucleic acids to synthesize chimeric oligomers. Owing to their special structures and the uncharged property, the oligomers with DNA analogues are useful in many applications, like fluorescence in situ hybridization (FISH), biosensors, gene chips, etc. In this study, we try to investigate the effect of an uncharged phosphate-methylated nucleotide embedded on the aptamer sequence with high affinity to IgG1 by using the computational approach. The simulation results predict that the embedded phosphate-methylated nucleotide can cause the changes in the tertiary structure and spatial charge distribution of aptamer and further influence the binding between the aptamer and IgG1. From this study, we obtain an aptamer modified with the phosphate-methylated nucleotide, named as Apt8#n10, can have an improved binding affinity to IgG1. According to these consequences, the embedded phosphate-methylated nucleotide can play a role in the aptamer sequence for tuning the binding affinity of the aptamer to its target molecule.