Modelling Drug-Target Binding Affinity using a BERT based Graph Neural network

Mark Lennox, Neil Robertson, Barry Devereux

Research output: Contribution to journalArticlepeer-review

Abstract

Understanding the interactions between novel drugs and target proteins is fundamentally important in disease research as discovering drug-protein interactions can be an exceptionally time-consuming and expensive process. Alternatively, this process can be simulated using modern deep learning methods that have the potential of utilising vast quantities of data to reduce the cost and time required to provide accurate predictions. We seek to leverage a set of BERT-style models that have been pre-trained on vast quantities of both protein and drug data. The encodings produced by each model are then utilised as node representations for a graph convolutional neural network, which in turn are used to model the interactions without the need to simultaneously fine-tune both protein and drug BERT models to the task. We evaluate the performance of our approach on two drug-target interaction datasets that were previously used as benchmarks in recent work.Our results significantly improve upon a vanilla BERT baseline approach as well as the former state-of-the-art methods for each task dataset. Our approach builds upon past work in two key areas; firstly, we take full advantage of two large pre-trained BERT models that provide improved representations of task-relevant properties of both drugs and proteins. Secondly, inspired by work in natural language processing that investigates how linguistic structure is represented in such models, we perform interpretability analyses that allow us to locate functionally-relevant areas of interest within each drug and protein. By modelling the drug-target interactions as a graph as opposed to a set of isolated interactions, we demonstrate the benefits of combining large pre-trained models and a graph neural network to make state-of-the-art predictions on drug-target binding affinity.

ASJC Scopus subject areas

  • Medicine(all)

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