Analysis and understanding of aptamer and peptide molecular interactions: Application to mucin 1 (Muc1) aptasensor

Molecular level interactions and accessibility to binding site play a critical role in efficacy of biosensors. Details on the orientation and location of binding of a biomarker to a bioreceptor can be obtained through computational modeling and analysis. In the present paper, Molecular Dynamics (MD) was used to model the and understand the molecular interaction within a aptamer based sensor using a known peptide-aptamer combination of anti-mucin 1 S2.2 aptamer and MUC1-G (ADPTRPAPG) peptide in a 150mM NaCl solution to mirror SPR aptasensor conditions. The modeling analysis was further extended to understand the influence of other solvent environments. In the solvent environment of 150mM NaCl, MUC1-G binding event was found to occur consistently in the loop region of the aptamer, and showed a key role of arginine residue of the peptide in the aptamer-peptide binding. To further emulate relevant biosensor application characteristics, variation in aptamer and peptide structure as well as solvent conditions were studied and analyzed. These illustrated the sensitivity and selectivity of MUC1-G peptide-aptamer binding. Selective changes in the solvent conditions to reflect a variety of physiological conditions that can be experienced in biosensor applications were modeled through modifications in the peptide-aptamer-solvent molecular systems. Results indicate that certain modified solvent conditions did not induce binding, but rather association events. Present results indicate even variations in the solvent conditions for biosensor applications can impact the binding. Insights from modeling and analysis illustrate the selectiveness and sensitivity to solvent environments in the case of Mucin 1, a breast cancer biomarker, which are critical to the development of reliable and repeatable biosensors.