Jian Wu

Zui Chen, Yansen Jing, Shengcheng Yuan et al.

Synthesizer is a type of electronic musical instrument that is now widely used in modern music production and sound design. Each parameters configuration of a synthesizer produces a unique timbre and can be viewed as a unique instrument. The problem of estimating a set of parameters configuration that best restore a sound timbre is an important yet complicated problem, i.e.: the synthesizer parameters estimation problem. We proposed a multi-modal deep-learning-based pipeline Sound2Synth, together with a network structure Prime-Dilated Convolution (PDC) specially designed to solve this problem. Our method achieved not only SOTA but also the first real-world applicable results on Dexed synthesizer, a popular FM synthesizer.

Yiheng Zhu, Jialu Wu, Qiuyi Li et al.

Inverse protein folding is a fundamental task in computational protein design, which aims to design protein sequences that fold into the desired backbone structures. While the development of machine learning algorithms for this task has seen significant success, the prevailing approaches, which predominantly employ a discriminative formulation, frequently encounter the error accumulation issue and often fail to capture the extensive variety of plausible sequences. To fill these gaps, we propose Bridge-IF, a generative diffusion bridge model for inverse folding, which is designed to learn the probabilistic dependency between the distributions of backbone structures and protein sequences. Specifically, we harness an expressive structure encoder to propose a discrete, informative prior derived from structures, and establish a Markov bridge to connect this prior with native sequences. During the inference stage, Bridge-IF progressively refines the prior sequence, culminating in a more plausible design. Moreover, we introduce a reparameterization perspective on Markov bridge models, from which we derive a simplified loss function that facilitates more effective training. We also modulate protein language models (PLMs) with structural conditions to precisely approximate the Markov bridge process, thereby significantly enhancing generation performance while maintaining parameter-efficient training. Extensive experiments on well-established benchmarks demonstrate that Bridge-IF predominantly surpasses existing baselines in sequence recovery and excels in the design of plausible proteins with high foldability. The code is available at https://github.com/violet-sto/Bridge-IF.

Zitai Kong, Yiheng Zhu, Yinlong Xu et al.

The design of protein sequences with desired functionalities is a fundamental task in protein engineering. Deep generative methods, such as autoregressive models and diffusion models, have greatly accelerated the discovery of novel protein sequences. However, these methods mainly focus on local or shallow residual semantics and suffer from low inference efficiency, large modeling space and high training cost. To address these challenges, we introduce ProtFlow, a fast flow matching-based protein sequence design framework that operates on embeddings derived from semantically meaningful latent space of protein language models. By compressing and smoothing the latent space, ProtFlow enhances performance while training on limited computational resources. Leveraging reflow techniques, ProtFlow enables high-quality single-step sequence generation. Additionally, we develop a joint design pipeline for the design scene of multichain proteins. We evaluate ProtFlow across diverse protein design tasks, including general peptides and long-chain proteins, antimicrobial peptides, and antibodies. Experimental results demonstrate that ProtFlow outperforms task-specific methods in these applications, underscoring its potential and broad applicability in computational protein sequence design and analysis.

Mingze Yin, Hanjing Zhou, Jialu Wu et al.

Antibodies safeguard our health through their precise and potent binding to specific antigens, demonstrating promising therapeutic efficacy in the treatment of numerous diseases, including COVID-19. Recent advancements in biomedical language models have shown the great potential to interpret complex biological structures and functions. However, existing antibody specific models have a notable limitation that they lack explicit consideration for antibody structural information, despite the fact that both 1D sequence and 3D structure carry unique and complementary insights into antibody behavior and functionality. This paper proposes Sequence-Structure multi-level pre-trained Antibody Language Model (S$^2$ALM), combining holistic sequential and structural information in one unified, generic antibody foundation model. We construct a hierarchical pre-training paradigm incorporated with two customized multi-level training objectives to facilitate the modeling of comprehensive antibody representations. S$^2$ALM's representation space uncovers inherent functional binding mechanisms, biological evolution properties and structural interaction patterns. Pre-trained over 75 million sequences and 11.7 million structures, S$^2$ALM can be adopted for diverse downstream tasks: accurately predicting antigen-antibody binding affinities, precisely distinguishing B cell maturation stages, identifying antibody crucial binding positions, and specifically designing novel coronavirus-binding antibodies. Remarkably, S$^2$ALM outperforms well-established and renowned baselines and sets new state-of-the-art performance across extensive antibody specific understanding and generation tasks. S$^2$ALM's ability to model comprehensive and generalized representations further positions its potential to advance real-world therapeutic antibody development, potentially addressing unmet academic, industrial, and clinical needs.