Abstract
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.
Highlights
Prostate specific antigen (PSA) is a glycoprotein and has a molecular weight of 33-34 kDa
The results of simulation and experiment are not fully consistent, the experimental results show that most of these selected aptamer sequences can react with PSA and produce significant signal changes in the frequency of quartz crystal microbalance (QCM) chip
Molecular simulation results gave us information to exclude aptamers that were predicted with poor binding to PSA from aptamer candidates, which effectively reduced the number of experiments in the aptamer selection
Summary
Prostate specific antigen (PSA) is a glycoprotein and has a molecular weight of 33-34 kDa. Patients with prostate cancer generally have a large amount and a high concentration of PSA released into their circulatory system; as a result, their serum PSA concentration is 105 times higher than that of regular healthy people. Measuring serum PSA concentration is commonly used in the early diagnosis and for subsequent monitoring of patients with prostate cancer. Patients who undergo an examination and show a serum PSA concentration ≥ 4.0 ng/mL [1, 2] are suspected of having prostate cancer, after which doctors will ask the patients to have regular follow-up examinations. If the PSA concentrations of patients are over 10 ng/mL, the doctors will ask the patients to take a biopsy to confirm whether they truly have prostate cancer. PSA testing is crucial for determining whether an individual has prostate cancer, and most assays for PSA detection are based on the use of antibodies as the recognition elements [3]
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