Date of Completion

2024

Document Type

Thesis

Degree Name

Bachelor of Science in Biochemistry

Keywords

Prostate Cancer

Abstract

In the pursuit of novel aptamers targeting the transmembrane protein glutamate carboxypeptidase II (GCPII), prominently expressed on prostate cancer cell lines, an in-silico design strategy was employed to circumvent the traditional SELEX approach. Thus, in order to design an aptamer that binds to GCPII for the early diagnosis of prostate cancer, the researchers employed an array of web servers and software tools, including the tRNA Database, HDOCK, PLIP, UNAfold, 3dRNA/DNA, BIOVIA Discovery Studio, and Chimera, to design aptamers with superior binding affinity and specificity. Screening 249 initial aptamer sequences using the tRNA Database and HDOCK simulations identified five candidates, with two modified to exhibit higher binding scores than the reference aptamer (A9g) when docked to GCPII, and PLIP analysis revealed critical binding hotspots for further modifications. As a result, among the five potential aptamer candidates obtained, two were successfully modified. From which were aptamers Zai-M18, Ram-M11, and Ram-M16 were successfully designed with docking score values of -327.22 kcal/mol, -326.26 kcal/mol, and -341.27 kcal/mol, respectively, to GCPII exceeding the docking score of A9g which was -324.03 kcal/mol, possibly accounting for the new hydrophobic interactions found on Zai-M18, Ram-M11, and Ram-M16, as compared to the pre-existing interactions of A9g with GCPII. That is why for future studies, it is recommended to do further molecular modifications on aptamers ZaiM18, Ram-M11, and Ram-M16, specifically enhancing their functional groups for the improvement of interactions with the utilization of molecular dynamics. Moreover, they could also be utilized in isothermal calorimetry titration in vitro studies.

First Advisor

Margel C. Bonifacio

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