Ensemble of local and global information for Protein–Ligand Binding Affinity Prediction

Abstract

Accurately predicting protein–ligand binding affinities is crucial for determining molecular properties and understanding their physical effects. Neural networks and transformers are the predominant methods for sequence modeling, and both have been successfully applied independently for protein–ligand binding affinity prediction. As local and global information of molecules are vital for protein–ligand binding affinity prediction, we aim to combine bi-directional gated recurrent unit (BiGRU) and convolutional neural network (CNN) to effectively capture both local and global molecular information. Additionally, attention mechanisms can be incorporated to automatically learn and adjust the level of attention given to local and global information, thereby enhancing the performance of the model. To achieve this, we propose the PLAsformer approach, which encodes local and global information of molecules using 3DCNN and BiGRU with attention mechanism, respectively. This approach enhances the model’s ability to encode comprehensive local and global molecular information.PLAsformer achieved a Pearson’s correlation coefficient of 0.812 and a Root Mean Square Error (RMSE) of 1.284 when comparing experimental and predicted affinity on the PDBBind-2016 dataset. These results surpass the current state-of-the-art methods for binding affinity prediction. The high accuracy of PLAsformer’s predictive performance, along with its excellent generalization ability, is clearly demonstrated by these findings.