Yueyang Huang

Shanzhuo Zhang, Zhiyuan Yan, Yueyang Huang et al.

Accurate ADMET (an abbreviation for "absorption, distribution, metabolism, excretion, and toxicity") predictions can efficiently screen out undesirable drug candidates in the early stage of drug discovery. In recent years, multiple comprehensive ADMET systems that adopt advanced machine learning models have been developed, providing services to estimate multiple endpoints. However, those ADMET systems usually suffer from weak extrapolation ability. First, due to the lack of labelled data for each endpoint, typical machine learning models perform frail for the molecules with unobserved scaffolds. Second, most systems only provide fixed built-in endpoints and cannot be customised to satisfy various research requirements. To this end, we develop a robust and endpoint extensible ADMET system, HelixADMET (H-ADMET). H-ADMET incorporates the concept of self-supervised learning to produce a robust pre-trained model. The model is then fine-tuned with a multi-task and multi-stage framework to transfer knowledge between ADMET endpoints, auxiliary tasks, and self-supervised tasks. Our results demonstrate that H-ADMET achieves an overall improvement of 4%, compared with existing ADMET systems on comparable endpoints. Additionally, the pre-trained model provided by H-ADMET can be fine-tuned to generate new and customised ADMET endpoints, meeting various demands of drug research and development requirements.

Jie Gao, Jing Hu, Shanzhuo Zhang et al.

Antibody engineering is essential for developing therapeutics and advancing biomedical research. Traditional discovery methods often rely on time-consuming and resource-intensive experimental screening. To enhance and streamline this process, we introduce a production-grade, high-throughput platform built on HelixFold3, HelixDesign-Antibody, which utilizes the high-accuracy structure prediction model, HelixFold3. The platform facilitates the large-scale generation of antibody candidate sequences and evaluates their interaction with antigens. Integrated high-performance computing (HPC) support enables high-throughput screening, addressing challenges such as fragmented toolchains and high computational demands. Validation on multiple antigens showcases the platform's ability to generate diverse and high-quality antibodies, confirming a scaling law where exploring larger sequence spaces increases the likelihood of identifying optimal binders. This platform provides a seamless, accessible solution for large-scale antibody design and is available via the antibody design page of PaddleHelix platform.

Jie Gao, Jun Li, Jing Hu et al.

Protein binder design is central to therapeutics, diagnostics, and synthetic biology, yet practical deployment remains challenging due to fragmented workflows, high computational costs, and complex tool integration. We present HelixDesign-Binder, a production-grade, high-throughput platform built on HelixFold3 that automates the full binder design pipeline, from backbone generation and sequence design to structural evaluation and multi-dimensional scoring. By unifying these stages into a scalable and user-friendly system, HelixDesign-Binder enables efficient exploration of binder candidates with favorable structural, energetic, and physicochemical properties. The platform leverages Baidu Cloud's high-performance infrastructure to support large-scale design and incorporates advanced scoring metrics, including ipTM, predicted binding free energy, and interface hydrophobicity. Benchmarking across six protein targets demonstrates that HelixDesign-Binder reliably produces diverse and high-quality binders, some of which match or exceed validated designs in predicted binding affinity. HelixDesign-Binder is accessible via an interactive web interface in PaddleHelix platform, supporting both academic research and industrial applications in antibody and protein binder development.

Zhiyuan Chen, Xiaomin Fang, Zixu Hua et al.

Efficient exploration of the chemical space to search the candidate drugs that satisfy various constraints is a fundamental task of drug discovery. Advanced deep generative methods attempt to optimize the molecules in the compact latent space instead of the discrete original space, but the mapping between the original and latent spaces is always kept unchanged during the entire optimization process. The unchanged mapping makes those methods challenging to fast adapt to various optimization scenes and leads to the great demand for assessed molecules (samples) to provide optimization direction, which is a considerable expense for drug discovery. To this end, we design a sample-efficient molecular generative method, HelixMO, which explores the scene-sensitive latent space to promote sample efficiency. The scene-sensitive latent space focuses more on modeling the promising molecules by dynamically adjusting the space mapping by leveraging the correlations between the general and scene-specific characteristics during the optimization process. Extensive experiments demonstrate that HelixMO can achieve competitive performance with only a few assessed samples on four molecular optimization scenes. Ablation studies verify the positive impact of the scene-specific latent space, which is capable of identifying the critical characteristics of the promising molecules. We also deployed HelixMO on the website PaddleHelix (https://paddlehelix.baidu.com/app/drug/drugdesign/forecast) to provide drug design service.