Aptasensors utilize aptamers as bioreceptors. Aptamers are highly efficient, 
have a high specificity and are reusable. Within the biosensor the aptamers are 
immobilized to maximize their access to target molecules. Knowledge of the 
orientation and location of the aptamer and peptide during binding could be 
gained through computational modeling. Experimentally, the aptamer (anti-MUC1 
S2.2) has been identified as a bioreceptor for breast cancer biomarker mucin 1 
(MUC1) protein. However, within this protein lie several peptide variants with 
the common sequence APDTRPAP that are targeted by the aptamer. Understanding 
orientation and location of the binding region for a peptide-aptamer complex is 
critical in their biosensor applicability. In this study, we investigate through 
computational modeling how this peptide sequence and its minor variants affect 
the peptide-aptamer complex binding. We use molecular dynamics simulations to 
study multiple peptide-aptamer systems consisting of MUC1 (APDTRPAP) and MUC1-G 
(APDTRPAPG) peptides with the anti-MUC1 aptamer under similar physiological 
conditions reported experimentally. Multiple simulations of the MUC1 peptide and 
aptamer reveal that the peptide interacts between 3' and 5' ends of the aptamer 
but does not fully bind. Multiple simulations of the MUC1-G peptide indicate 
consistent binding with the thymine loop of the aptamer, initiated by the 
arginine residue of the peptide. We find that the binding event induces 
structural changes in the aptamer by altering the number of hydrogen bonds 
within the aptamer and establishes a stable peptide-aptamer complex. In all 
MUC1-G cases the occurrence of binding was confirmed by systematically studying 
the distance distributions between peptide and aptamers. These results are found 
to corroborate well with experimental study reported in the literature that 
indicated a strong binding in the case of MUC1-G peptide and anti-MUC1 aptamer. 
Present MD simulations highlight the role of the arginine residue of MUC1-G 
peptide in initiating the binding. The addition of the glycine residue to the 
peptide, as in the case of MUC1-G, is shown to yield a stable binding. Our study 
clearly demonstrates the ability of MD simulations to obtain molecular insights 
for peptide-aptamer binding, and to provide details on the orientation and 
location of binding between the peptide-aptamer that can be instrumental in 
biosensor development.