Zitong Tian

Ziyi Yang, Zitong Tian, Yinjun Jia et al.

D-peptide binders targeting L-proteins have promising therapeutic potential. Despite rapid advances in machine learning-based target-conditioned peptide design, generating D-peptide binders remains largely unexplored. In this work, we show that by injecting axial features to $E(3)$-equivariant (polar) vector features,it is feasible to achieve cross-chirality generalization from homo-chiral (L--L) training data to hetero-chiral (D--L) design tasks. By implementing this method within a latent diffusion model, we achieved D-peptide binder design that not only outperforms existing tools in in silico benchmarks, but also demonstrates efficacy in wet-lab validation. To our knowledge, our approach represents the first wet-lab validated generative AI for the de novo design of D-peptide binders, offering new perspectives on handling chirality in protein design.

Juncai He, Xinliang Liu, Zitong Tian

This paper studies the numerical approximation of divergence-free vector fields by linearized shallow neural networks, also referred to as random feature models or finite neuron spaces. Combining the stable potential lifting for divergence-free fields with the scalar Sobolev integral representation theory via ReLU$^k$ networks, we derive a core integral representation of divergence-free Sobolev vector fields through antisymmetric potentials parameterized by linearized ReLU$^k$ neural networks. This representation, together with a quasi-uniform distribution argument for the inner parameters, yields optimal approximation rates for such linearized ReLU$^k$ neural networks under an exact divergence-free constraint. Numerical experiments in two and three spatial dimensions, including $L^2$ projection and steady Stokes problems, confirm the theoretical rates and illustrate the effectiveness of exactly divergence-free conditions in computation.

Zitao Chen, Yinjun Jia, Zitong Tian et al.

Medicinal chemists often optimize drugs considering their 3D structures and designing structurally distinct molecules that retain key features, such as shapes, pharmacophores, or chemical properties. Previous deep learning approaches address this through supervised tasks like molecule inpainting or property-guided optimization. In this work, we propose a flexible zero-shot molecule manipulation method by navigating in a shared latent space of 3D molecules. We introduce a Variational AutoEncoder (VAE) for 3D molecules, named MolFLAE, which learns a fixed-dimensional, E(3)-equivariant latent space independent of atom counts. MolFLAE encodes 3D molecules using an E(3)-equivariant neural network into fixed number of latent nodes, distinguished by learned embeddings. The latent space is regularized, and molecular structures are reconstructed via a Bayesian Flow Network (BFN) conditioned on the encoder's latent output. MolFLAE achieves competitive performance on standard unconditional 3D molecule generation benchmarks. Moreover, the latent space of MolFLAE enables zero-shot molecule manipulation, including atom number editing, structure reconstruction, and coordinated latent interpolation for both structure and properties. We further demonstrate our approach on a drug optimization task for the human glucocorticoid receptor, generating molecules with improved hydrophilicity while preserving key interactions, under computational evaluations. These results highlight the flexibility, robustness, and real-world utility of our method, opening new avenues for molecule editing and optimization.