Organic photovoltaic (OPV) materials offer a promising pathway for sustainable energy generation. However, their development is hindered by the challenge of identifying high-performance donor-acceptor pairs with optimal power conversion efficiencies (PCEs). Most existing design strategies focus exclusively on either the donor or the acceptor, rather than employing a unified model capable of designing both components. In this work, we introduce a dual-pronged machine learning framework for OPV discovery, integrating predictive modeling and generative molecular design. In this study, we propose the newly curated Organic Photovoltaic Donor-Acceptor Dataset (OPV²D), the largest of its kind, comprising 2,000 experimentally characterized donor-acceptor pairs. This dataset serves as a comprehensive foundation for model training and evaluation. To enable accurate property prediction in organic photovoltaic (OPV) materials, we first introduce the Organic Photovoltaic Classifier (OPVC) to predict the likelihood that a given material exhibits OPV behavior. Complementing this, we develop a hierarchical graph neural network framework that integrates multi-task learning and cross-modal donor–acceptor interaction modeling. This framework includes the Molecular Orbital Energy Estimator (MOE²) for predicting the highest occupied molecular orbital–lowest unoccupied molecular orbital (HOMO–LUMO) energy levels, and the Photovoltaic Performance Predictor (P³) for estimating power conversion efficiency (PCE). In addition, we introduce the Material Generative Pretrained Transformer (MatGPT) to generate synthetically accessible organic semiconductors. Building on this, we propose a reinforcement learning strategy with three-objective policy optimization that guides molecular generation while preserving chemical validity. By bridging molecular representation learning with device performance prediction, our framework advances computational OPV material discovery.

Structure-based drug discovery, encompassing the tasks of protein-ligand docking and pocket-aware 3D drug design, represents a core challenge in drug discovery. However, no existing work can deal with both tasks to effectively leverage the duality between them, and current methods for each task are hindered by challenges in modeling 3D information and the limitations of available data. To address these issues, we propose 3DMolFormer, a unified dual-channel transformer-based framework applicable to both docking and 3D drug design tasks, which exploits their duality by utilizing docking functionalities within the drug design process. Specifically, we represent 3D pocket-ligand complexes using parallel sequences of discrete tokens and continuous numbers, and we design a corresponding dual-channel transformer model to handle this format, thereby overcoming the challenges of 3D information modeling. Additionally, we alleviate data limitations through large-scale pre-training on a mixed dataset, followed by supervised and reinforcement learning fine-tuning techniques respectively tailored for the two tasks. Experimental results demonstrate that 3DMolFormer outperforms previous approaches in both protein-ligand docking and pocket-aware 3D drug design, highlighting its promising application in structure-based drug discovery. The code is available at: https://github.com/HXYfighter/3DMolFormer.

Gradient regularization (GR), which aims to penalize the gradient norm atop the loss function, has shown promising results in training modern over-parameterized deep neural networks. However, can we trust this powerful technique? This paper reveals that GR can cause performance degeneration in adaptive optimization scenarios, particularly with learning rate warmup. Our empirical and theoretical analyses suggest this is due to GR inducing instability and divergence in gradient statistics of adaptive optimizers at the initial training stage. Inspired by the warmup heuristic, we propose three GR warmup strategies, each relaxing the regularization effect to a certain extent during the warmup course to ensure the accurate and stable accumulation of gradients. With experiments on Vision Transformer family, we confirm the three GR warmup strategies can effectively circumvent these issues, thereby largely improving the model performance. Meanwhile, we note that scalable models tend to rely more on the GR warmup, where the performance can be improved by up to 3% on Cifar10 compared to baseline GR. Code is available at https://github.com/zhaoyang-0204/gnp.

*De novo* drug design is a pivotal issue in pharmacology and a new area of focus in AI for science research. A central challenge in this field is to generate molecules with specific properties while also producing a wide range of diverse candidates. Although advanced technologies such as transformer models and reinforcement learning have been applied in drug design, their potential has not been fully realized. Therefore, we propose MolRL-MGPT, a reinforcement learning algorithm with multiple GPT agents for drug molecular generation. To promote molecular diversity, we encourage the agents to collaborate in searching for desirable molecules in diverse directions. Our algorithm has shown promising results on the GuacaMol benchmark and exhibits efficacy in designing inhibitors against SARS-CoV-2 protein targets. The codes are available at: https://github.com/HXYfighter/MolRL-MGPT.

How to train deep neural networks (DNNs) to generalize well is a central concern in deep learning, especially for severely overparameterized networks nowadays. In this paper, we propose an effective method to improve the model generalization by additionally penalizing the gradient norm of loss function during optimization. We demonstrate that confining the gradient norm of loss function could help lead the optimizers towards finding flat minima. We leverage the first-order approximation to efficiently implement the corresponding gradient to fit well in the gradient descent framework. In our experiments, we confirm that when using our methods, generalization performance of various models could be improved on different datasets. Also, we show that the recent sharpness-aware minimization method (Foretet al., 2021) is a special, but not the best, case of our method, where the best case of our method could give new state-of-art performance on these tasks. Code is available at https://github.com/zhaoyang-0204/gnp.