The Combination of Computational and Biosensing Technologies for Selecting Aptamer against Prostate Specific Antigen

Herein, we report a method of combining bioinformatics and biosensing technologies to select aptamers against prostate specific antigen (PSA). The main objective of this study is to select DNA aptamers with higher binding affinity for PSA by using the proposed method. Based on the five known sequences of PSA-binding aptamers, we adopted the functions of reproduction and crossover in the genetic algorithm to produce next-generation sequences for the computational and experimental analysis. RNAfold web server was utilized to analyze the secondary structures, and the 3-dimensional molecular models of aptamer sequences were generated by using RNAComposer web server. ZRANK scoring function was used to rerank the docking predictions from ZDOCK. The biosensors, the quartz crystal microbalance (QCM) and a surface plasmon resonance (SPR) instrument, were used to verify the binding ability of selected aptamer for PSA. By carrying out the simulations and experiments after two generations, we obtain one aptamer that can have the highest binding affinity with PSA, which generates almost 2-fold and 3-fold greater measured signals than the responses produced by the best known DNA sequence in the QCM and SPR experiments, respectively.