Abstract
Over a decade, efforts have been made to extend data science-based approaches to improve the process of drug-target interactions (DTIs) by modeling drugs and targets as graphs. From a drug discovery point of view, a pharmacophore, a subgraph of a drug candidate, is an essential structural and chemical feature necessary for interacting with a specific biological target. Effective identification of potential pharmacophores from a given candidate drug is a research issue. In the literature, efforts are being made to investigate machine learning and Graph Neural Network (GNN) based frameworks to identify the potential drug candidates for a given target. However, the problem of extracting the knowledge of the potential pharmacophore of the given candidate drug has not been explored. There is an opportunity to extract pharmacophores from drug candidates by exploiting the knowledge of potential subgraphs extracted through a trained GNN model. In this paper, we propose a two-phase GNN-based framework for identifying drug candidates and extracting potential pharmacophores from these candidates. The framework consists of two parts. First, we employ a GNN-based model to compute the affinity score for the given drug compound. Second, by employing the Monte Carlo Tree Search (MCTS) algorithm, the trained GNN is leveraged to extract potential subgraphs representing pharmacophores. The experimental results on the Davis, Kiba and Allergy datasets demonstrate the feasibility of the proposed approach to extract pharmacophores of candidate drugs with high performance. The predicted binding affinities of molecular subgraphs extracted from drug candidates are very similar to those of the corresponding drug candidates. The proposed approach helps explore the potential pharmacophore of the given candidate drug, which enhances the explainability of DTI to obtain deeper insights into crucial molecular interactions.