SSGraphCPI: A Novel Model for Predicting Compound-Protein Interactions Based on Deep Learning

Abstract

Identifying compound-protein (drug-target, DTI) interactions (CPI) accurately is a key step in drug discovery. Including virtual screening and drug reuse, it can significantly reduce the time it takes to identify drug candidates and provide patients with timely and effective treatment. Recently, more and more researchers have developed CPI's deep learning model, including feature representation of a 2D molecular graph of a compound using a graph convolutional neural network, but this method loses much important information about the compound. In this paper, we propose a novel three-channel deep learning framework, named SSGraphCPI, for CPI prediction, which is composed of recurrent neural networks with an attentional mechanism and graph convolutional neural network. In our model, the characteristics of compounds are extracted from 1D SMILES string and 2D molecular graph. Using both the 1D SMILES string sequence and the 2D molecular graph can provide both sequential and structural features for CPI predictions. Additionally, we select the 1D CNN module to learn the hidden data patterns in the sequence to mine deeper information. Our model is much more suitable for collecting more effective information of compounds. Experimental results show that our method achieves significant performances with RMSE (Root Mean Square Error) = 2.24 and R2 (degree of linear fitting of the model) = 0.039 on the GPCR (G Protein-Coupled Receptors) dataset, and with RMSE = 2.64 and R2 = 0.018 on the GPCR dataset RMSE, which preforms better than some classical deep learning models, including RNN/GCNN-CNN, GCNNet and GATNet.

Keywords: IC50 value; compound properties; compound-protein interactions; deep learning; protein preperties.

Figure 1

Loss value variation diagram of different models.

Figure 2

A 2D molecular diagram of the top three compounds.

Figure 3

A 3D molecular diagram of the top three compounds.

Figure 4

Docking diagram of C₃₄H₃₀N₄O₂S₂ molecule and EGF receptor protein.

Figure 5

The overall flow chart of the SSGraphCPI model.

Figure 6

Network diagram of the protein feature vectors extraction.