Liyang Xie

Liyang Xie, Haoran Zhang, Zhendong Wang et al.

Diffusion- and flow-based generative models have recently demonstrated strong performance in protein backbone generation tasks, offering unprecedented capabilities for de novo protein design. However, while achieving notable performance in generation quality, these models are limited by their generating speed, often requiring hundreds of iterative steps in the reverse-diffusion process. This computational bottleneck limits their practical utility in large-scale protein discovery, where thousands to millions of candidate structures are needed. To address this challenge, we explore the techniques of score distillation, which has shown great success in reducing the number of sampling steps in the vision domain while maintaining high generation quality. However, a straightforward adaptation of these methods results in unacceptably low designability. Through extensive study, we have identified how to appropriately adapt Score identity Distillation (SiD), a state-of-the-art score distillation strategy, to train few-step protein backbone generators which significantly reduce sampling time, while maintaining comparable performance to their pretrained teacher model. In particular, multistep generation combined with inference time noise modulation is key to the success. We demonstrate that our distilled few-step generators achieve more than a 20-fold improvement in sampling speed, while achieving similar levels of designability, diversity, and novelty as the Proteina teacher model. This reduction in inference cost enables large-scale in silico protein design, thereby bringing diffusion-based models closer to real-world protein engineering applications. The PyTorch implementation is available at https://github.com/LY-Xie/SiD_Protein

Liyang Xie, Kaixiang Lin, Shu Wang et al.

Generative Adversarial Network (GAN) and its variants have recently attracted intensive research interests due to their elegant theoretical foundation and excellent empirical performance as generative models. These tools provide a promising direction in the studies where data availability is limited. One common issue in GANs is that the density of the learned generative distribution could concentrate on the training data points, meaning that they can easily remember training samples due to the high model complexity of deep networks. This becomes a major concern when GANs are applied to private or sensitive data such as patient medical records, and the concentration of distribution may divulge critical patient information. To address this issue, in this paper we propose a differentially private GAN (DPGAN) model, in which we achieve differential privacy in GANs by adding carefully designed noise to gradients during the learning procedure. We provide rigorous proof for the privacy guarantee, as well as comprehensive empirical evidence to support our analysis, where we demonstrate that our method can generate high quality data points at a reasonable privacy level.