SAMG: State-Action-Aware Offline-to-Online Reinforcement Learning with Offline Model Guidance

The offline-to-online (O2O) paradigm in reinforcement learning (RL) utilizes pre-trained models on offline datasets for subsequent online fine-tuning. However, conventional O2O RL algorithms typically require maintaining and retraining the large offline datasets to mitigate the effects of out-of-distribution (OOD) data, which limits their efficiency in exploiting online samples. To address this challenge, we introduce a new paradigm called SAMG: State-Action-Conditional Offline-to-Online Reinforcement Learning with Offline Model Guidance. In particular, rather than directly training on offline data, SAMG freezes the pre-trained offline critic to provide offline values for each state-action pair to deliver compact offline information. This framework eliminates the need for retraining with offline data by freezing and leveraging these values of the offline model. These are then incorporated with the online target critic using a Bellman equation weighted by a policy state-action-aware coefficient. This coefficient, derived from a conditional variational auto-encoder (C-VAE), aims to capture the reliability of the offline data on a state-action level. SAMG could be easily integrated with existing Q-function based O2O RL algorithms. Theoretical analysis shows good optimality and lower estimation error of SAMG. Empirical evaluations demonstrate that SAMG outperforms four state-of-the-art O2O RL algorithms in the D4RL benchmark.

ETDock: A Novel Equivariant Transformer for Protein-Ligand Docking

Predicting the docking between proteins and ligands is a crucial and challenging task for drug discovery. However, traditional docking methods mainly rely on scoring functions, and deep learning-based docking approaches usually neglect the 3D spatial information of proteins and ligands, as well as the graph-level features of ligands, which limits their performance. To address these limitations, we propose an equivariant transformer neural network for protein-ligand docking pose prediction. Our approach involves the fusion of ligand graph-level features by feature processing, followed by the learning of ligand and protein representations using our proposed TAMformer module. Additionally, we employ an iterative optimization approach based on the predicted distance matrix to generate refined ligand poses. The experimental results on real datasets show that our model can achieve state-of-the-art performance.

Predicting Protein-Ligand Binding Affinity with Equivariant Line Graph Network

Binding affinity prediction of three-dimensional (3D) protein ligand complexes is critical for drug repositioning and virtual drug screening. Existing approaches transform a 3D protein-ligand complex to a two-dimensional (2D) graph, and then use graph neural networks (GNNs) to predict its binding affinity. However, the node and edge features of the 2D graph are extracted based on invariant local coordinate systems of the 3D complex. As a result, the method can not fully learn the global information of the complex, such as, the physical symmetry and the topological information of bonds. To address these issues, we propose a novel Equivariant Line Graph Network (ELGN) for affinity prediction of 3D protein ligand complexes. The proposed ELGN firstly adds a super node to the 3D complex, and then builds a line graph based on the 3D complex. After that, ELGN uses a new E(3)-equivariant network layer to pass the messages between nodes and edges based on the global coordinate system of the 3D complex. Experimental results on two real datasets demonstrate the effectiveness of ELGN over several state-of-the-art baselines.