What I've learned from 25 years of automated science, and what the future holds: an interview with Ross King We're excited to launch our new series, where we're speaking with leading researchers to explore the breakthroughs driving AI and the reality of the future promises - to give you an inside perspective on the headlines. Our first interviewee is Ross King, who created the first robot scientist back in 2009. He spoke to us about the nature of scientific discovery, the role AI has to play, and his recent work in DNA computing. Automated science is a really exciting area, and it feels like everyone's talking about it at the moment - e.g. But you've been working in this field for many years now. In 2009 you developed Adam, the first robot scientist to generate novel scientific knowledge. Could you tell me some more about that? So the history goes back to before Adam.

Recently, utilizing reinforcement learning (RL) to generate molecules with desired properties has been highlighted as apromising strategy for drug design.

Dual-target therapeutic strategies have become a compelling approach and attracted significant attention due to various benefits, such as their potential in overcoming drug resistance in cancer therapy. Considering the tremendous success that deep generative models have achieved in structure-based drug design in recent years, we formulate dual-target drug design as a generative task and curate a novel dataset of potential target pairs based on synergistic drug combinations. We propose to design dual-target drugs with diffusion models that are trained on single-target protein-ligand complex pairs. Specifically, we align two pockets in 3D space with protein-ligand binding priors and build two complex graphs with shared ligand nodes for SE(3)-equivariant composed message passing, based on which we derive a composed drift in both 3D and categorical probability space in the generative process. Our algorithm can well transfer the knowledge gained in single-target pretraining to dual-target scenarios in a zero-shot manner.

Drug design is a crucial step in the drug discovery cycle.

Diffusion models have emerged as a leading framework in generative modeling, poised to transform the traditionally slow and costly process of drug discovery. This review provides a systematic comparison of their application in designing two principal therapeutic modalities: small molecules and therapeutic peptides. We dissect how the unified framework of iterative denoising is adapted to the distinct molecular representations, chemical spaces, and design objectives of each modality. For small molecules, these models excel at structure-based design, generating novel, pocket-fitting ligands with desired physicochemical properties, yet face the critical hurdle of ensuring chemical synthesizability. Conversely, for therapeutic peptides, the focus shifts to generating functional sequences and designing de novo structures, where the primary challenges are achieving biological stability against proteolysis, ensuring proper folding, and minimizing immunogenicity. Despite these distinct challenges, both domains face shared hurdles: the scarcity of high-quality experimental data, the reliance on inaccurate scoring functions for validation, and the crucial need for experimental validation. We conclude that the full potential of diffusion models will be unlocked by bridging these modality-specific gaps and integrating them into automated, closed-loop Design-Build-Test-Learn (DBTL) platforms, thereby shifting the paradigm from mere chemical exploration to the on-demand engineering of novel~therapeutics.