KNU-DTI: KNowledge United Drug-Target Interaction prediction

Accurately predicting drug-target protein interactions (DTI) is a cornerstone of drug discovery, enabling the identification of potential therapeutic compounds. Sequence-based prediction models, despite their simplicity, hold great promise in extracting essential information directly from raw sequences. However, the focus in recent DTI studies has increasingly shifted toward enhancing algorithmic complexity, often at the expense of fully leveraging robust sequence representation learning methods. This shift has led to the underestimation and gradual neglect of methodologies aimed at effectively capturing discriminative features from sequences. Our work seeks to address this oversight by emphasizing the value of well-constructed sequence representation algorithms, demonstrating that even with simple interaction mapping algorithm techniques, accurate DTI models can be achieved. By prioritizing meaningful information extraction over excessive model complexity, we aim to advance the development of practical and generalizable DTI prediction frameworks.

We developed the KNowledge Uniting DTI model (KNU-DTI), which retrieves structural information and unites them. Protein structural properties were obtained using structural property sequence (SPS). Extended-connectivity fingerprint (ECFP) was used to estimate the structure-activity relationship in molecules. Including these two features, a total of five latent vectors were derived from protein and molecule via various neural networks and integrated by elemental-wise addition to predict binding interactions or affinity. Using four test concepts to evaluate the model, we show that the model outperforms recently published competitors. Finally, a case study indicated that our model has a competitive edge over existing docking simulations in some cases.