From thermodynamics to protein design: Diffusion models for biomolecule generation towards autonomous protein engineering

Protein design with desirable properties has been a significant challenge for many decades. Generative artificial intelligence is a promising approach and has achieved great success in various protein generation tasks. Notably, diffusion models stand out for their robust mathematical foundations and impressive generative capabilities, offering unique advantages in certain applications such as protein design. In this review, we first give the definition and characteristics of diffusion models and then focus on two strategies: Denoising Diffusion Probabilistic Models and Score-based Generative Models, where DDPM is the discrete form of SGM. Furthermore, we discuss their applications in protein design, peptide generation, drug discovery, and protein-ligand interaction. Finally, we outline the future perspectives of diffusion models to advance autonomous protein design and engineering. The E(3) group consists of all rotations, reflections, and translations in three-dimensions. The equivariance on the E(3) group can keep the physical stability of the frame of each amino acid as much as possible, and we reflect on how to keep the diffusion model E(3) equivariant for protein generation.

Evaluating The Robustness of Self-Supervised Representations to Background/Foreground Removal

Despite impressive empirical advances of SSL in solving various tasks, the problem of understanding and characterizing SSL representations learned from input data remains relatively under-explored. We provide a comparative analysis of how the representations produced by SSL models differ when masking parts of the input. Specifically, we considered state-of-the-art SSL pretrained models, such as DINOv2, MAE, and SwaV, and analyzed changes at the representation levels across 4 Image Classification datasets. First, we generate variations of the datasets by applying foreground and background segmentation. Then, we conduct statistical analysis using Canonical Correlation Analysis (CCA) and Centered Kernel Alignment (CKA) to evaluate the robustness of the representations learned in SSL models. Empirically, we show that not all models lead to representations that separate foreground, background, and complete images. Furthermore, we test different masking strategies by occluding the center regions of the images to address cases where foreground and background are difficult. For example, the DTD dataset that focuses on texture rather specific objects.