Does adding the drug-drug similarity to drug-target interaction prediction methods make a noticeable improvement in their efficiency?

Predicting drug-target interactions has become an important bioinformatics issue because it is one of the critical and preliminary stages of drug repositioning. Therefore, scientists are trying to develop more accurate computational methods for predicting drug-target interactions. These methods are usually based on machine learning or recommender systems and use biological and chemical information to improve the accuracy of predictions. In the background of these methods, there is a hypothesis that similar drugs have similar targets. So, the similarity between drugs as chemical information is added to the computational methods to improve the prediction results. The question that arises here is whether this claim is actually true? If so, what method should we use to calculate drug-drug similarities? Will we obtain the same improvement from any method we use?Here, we want to investigate this claimed positive effect. For this purpose, we consider different types of real similarities, random similarities, four important datasets and four state-of-the-art methods. Our results show that the type of data, the method which is used to predict the interactions, and the algorithm used to calculate the similarities are all important, and it cannot be easily stated that adding drug-drug similarities can significantly improve the results. Therefore, our results could suggest a checklist for scientists who want to improve their machine learning methods.