P2DFlow: A Protein Ensemble Generative Model with SE(3) Flow Matching

Biological processes, functions, and properties are intricately linked to the ensemble of protein conformations, rather than being solely determined by a single stable conformation. In this study, we have developed P2DFlow, a generative model based on SE(3) flow matching, to predict the structural ensembles of proteins. We specifically designed a valuable prior for the flow process and enhanced the model's ability to distinguish each intermediate state by incorporating an additional dimension to describe the ensemble data, which can reflect the physical laws governing the distribution of ensembles, so that the prior knowledge can effectively guide the generation process. When trained and evaluated on the MD datasets of ATLAS, P2DFlow outperforms other baseline models on extensive experiments, successfully capturing the observable dynamic fluctuations as evidenced in crystal structure and MD simulations. As a potential proxy agent for protein molecular simulation, the high-quality ensembles generated by P2DFlow could significantly aid in understanding protein functions across various scenarios. Code is available at https://github.com/BLEACH366/P2DFlow.

Continual Learning via Online Leverage Score Sampling

In order to mimic the human ability of continual acquisition and transfer of knowledge across various tasks, a learning system needs the capability for continual learning, effectively utilizing the previously acquired skills. As such, the key challenge is to transfer and generalize the knowledge learned from one task to other tasks, avoiding forgetting and interference of previous knowledge and improving the overall performance. In this paper, within the continual learning paradigm, we introduce a method that effectively forgets the less useful data samples continuously and allows beneficial information to be kept for training of the subsequent tasks, in an online manner. The method uses statistical leverage score information to measure the importance of the data samples in every task and adopts frequent directions approach to enable a continual or life-long learning property. This effectively maintains a constant training size across all tasks. We first provide mathematical intuition for the method and then demonstrate its effectiveness in avoiding catastrophic forgetting and computational efficiency on continual learning of classification tasks when compared with the existing state-of-the-art techniques.