Computer-aided design of aptamers for SMMC-7721 liver carcinoma cells

Abstract

Abstract Objective A pattern recognition model was developed for aptamers against SMMC-7721 by applying the support vector machine (SVM) algorithm. Subsequently, according to computer-aided aptamer design, eight DNA aptamer sequences were synthesized and tested. Methods Candidate aptamer sequences selected for SMMC-7721 liver carcinoma cells were obtained with whole cell-SELEX. Their reverse-complement sequences were used for descriptor calculation to develop structure-activity relationships (SAR) model. SVM was adopted for the pattern recognition for candidate aptamer sequences with high or low affinity against SMMC-7721 liver carcinoma cells. By the model predictions, we designed, synthesized and tested eight DNA aptamer sequences against SMMC-7721. Results Five molecular descriptors from reverse-complement sequences were obtained to develop the SAR model of pattern recognition. The predicted fractions of winner aptamers with high affinity for the 3rd, 5th, 7th, 9th, 11th, and 13th rounds of SELEX selection are 0.09, 0.17, 0.69, 0.84, 0.90 and 0.98, respectively. Their fitting curve and the corresponding exponential equation conform to the aptamer evolutionary principles of SELEX based screening. These new designed sequences belonging to the class of sequences with high binding affinity have experimental dissociation constants K d in the nanomolar range. Conclusion The feasibility of applying computer-aided aptamer design has been demonstrated.