RefinePocket: An Attention-Enhanced and Mask-Guided Deep Learning Approach for Protein Binding Site Prediction.

Protein binding site prediction is an important prerequisite task of drug discovery and design. While binding sites are very small, irregular and varied in shape, making the prediction very challenging. Standard 3D U-Net has been adopted to predict binding sites but got stuck with unsatisfactory prediction results, incomplete, out-of-bounds, or even failed. The reason is that this scheme is less capable of extracting the chemical interactions of the entire region and hardly takes into account the difficulty of segmenting complex shapes. In this paper, we propose a refined U-Net architecture, called RefinePocket, consisting of an attention-enhanced encoder and a mask-guided decoder. During encoding, taking binding site proposal as input, we employ Dual Attention Block (DAB) hierarchically to capture rich global information, exploring residue relationship and chemical correlations in spatial and channel dimensions respectively. Then, based on the enhanced representation extracted by the encoder, we devise Refine Block (RB) in the decoder to enable self-guided refinement of uncertain regions gradually, resulting in more precise segmentation. Experiments show that DAB and RB complement and promote each other, making RefinePocket has an average improvement of 10.02% on DCC and 4.26% on DVO compared with the state-of-the-art method on four test sets.