Hierarchical Contrastive Learning for Multi-Domain Protein-Ligand Binding

Predicting protein-ligand binding affinity remains intractable for multi-domain proteins, where inter-domain dynamics govern molecular recognition. Existing geometric deep learning methods typically treat proteins as monolithic static graphs, suffering from rigid-body assumptions and aleatoric noise in flexible regions. To address this, we introduced HCLBind, a self-supervised framework that decouples geometric representation learning from affinity regression. HCLBind leverages a general-to-specific pre-training paradigm on the Q-BioLiP database to learn a robust physical grammar of binding. We propose a novel hierarchical decoy strategy: the model learns local physicochemical constraints through protein coordinate perturbation in single-domain proteins and global conformational geometry through inter-domain rotation in multi-domain complexes. Our hybrid architecture integrates a domain-gated graph attention network and cross-modal attention to explicitly prioritize domain interfaces. Furthermore, we employ LoRA on protein and ligand foundation models, ensuring efficient optimization while preserving evolutionary knowledge. Experiments on PDBBind demonstrate that HCLBind effectively learns discriminative interface features and provides robust uncertainty estimation, overcoming the limitations of standard supervised learning. The code is available at https://github.com/jiankliu/HCLBind.

The Brain-Inspired Decoder for Natural Visual Image Reconstruction

Decoding images from brain activity has been a challenge. Owing to the development of deep learning, there are available tools to solve this problem. The decoded image, which aims to map neural spike trains to low-level visual features and high-level semantic information space. Recently, there are a few studies of decoding from spike trains, however, these studies pay less attention to the foundations of neuroscience and there are few studies that merged receptive field into visual image reconstruction. In this paper, we propose a deep learning neural network architecture with biological properties to reconstruct visual image from spike trains. As far as we know, we implemented a method that integrated receptive field property matrix into loss function at the first time. Our model is an end-to-end decoder from neural spike trains to images. We not only merged Gabor filter into auto-encoder which used to generate images but also proposed a loss function with receptive field properties. We evaluated our decoder on two datasets which contain macaque primary visual cortex neural spikes and salamander retina ganglion cells (RGCs) spikes. Our results show that our method can effectively combine receptive field features to reconstruct images, providing a new approach to visual reconstruction based on neural information.