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In order to optimize the performance of the PPIs prediction methods, we used the dropout method to reduce over-fitting by deep neural networks (DNNs), and combined with three types of feature extraction methods, conjoint triad (CT), auto covariance (AC) and local descriptor (LD), to build DNN models based on amino acid sequences. The results showed that the accuracy of the CT, AC and LD increased from 97.11% to 98.12%, 96.84% to 98.17%, and 95.30% to 95.60%, respectively. The loss values of the CT, AC and LD decreased from 27.47% to 14.96%, 65.91% to 17.82% and 36.23% to 15.34%, respectively. Experimental results show that dropout can optimize the performances of the DNN models. The results can provide a resource for scholars in future studies involving the prediction of PPIs. 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