Nuclera & leadXpro Partner to Accelerate Structure-Based Drug Design for Complex Membrane Proteins


Nuclera and leadXpro recently announced a scientific partnership. The collaboration brings together eProtein Discovery’s rapid multiplex membrane protein screening with leadXpro’s AI/ML-driven construct design and membrane protein expertise to advance structural studies and therapeutic development.

Membrane proteins remain among the most valuable yet difficult to obtain drug targets. These proteins are notoriously challenging to express and purify in sufficient quantity and quality for structural biology and biophysical studies, limiting drug discovery programs even when promising biology is well understood.

Integrating eProtein Discovery’s Cell-Free Protein Synthesis multiplex screening technology with leadXpro’s AI/ML and biophysical and structural characterization expertise, the partnership will establish an AI-guided, iterative, end-to-end workflow. The workflow will link in silico construct design with rapid, experimental multiplex screening to accelerate and de-risk challenging membrane protein programs, shortening the path to structural and biophysical insights for structure-based drug discovery.

Membrane protein constructs will be screened using Nuclera’s eProtein Discovery System with the most promising variants undergoing detailed biophysical characterization and high-resolution cryo-EM structure determination led by leadXpro. Insights from these studies will be integrated into AI/ML models for construct design and stability predictions, improving yields, functionality, and success rates. The partnership will also inform future integration of AI/ML capabilities into Nuclera’s product portfolio to embed predictive design into the eProtein Discovery System, and strengthen leadXpro’s platform in rapidly producing and characterizing difficult membrane protein targets.

Dr. Michael Chen, CEO and co-founder, Nuclera, said “Scientists are under pressure to progress increasingly complex membrane protein programs faster. By partnering with leadXpro, we can pair AI/ML-driven construct design with our rapid multiplex membrane protein screening to provide a truly ‘lab-in-loop’ workflow. This collaboration is an important step towards embedding AI/ML into Nuclera’s system so that researchers can go from sequence to high-value structural and functional insights in a fraction of the time currently required.”

Dr. Michael Hennig, CEO, leadXpro, added “Access to well-optimized membrane protein constructs is critical for producing high-quality proteins that enable biophysical and structural biology studies. Nuclera’s eProtein Discovery platform provides a robust, rapid, and reproducible approach to exploring construct space. Combined with our established AI/ML and structural biology expertise, this integration allows us to support better design decisions earlier and accelerate the progression of promising drug candidates.”

Nuclera’s mission is to accelerate discovery by providing researchers rapid, easy access to the highest-quality functional proteins essential for drug discovery research. The Company’s eProtein Discovery benchtop system combines unique cell-free expression systems, novel digital microfluidics, and robust screening data to empower scientists to perform multiplex protein screening, characterization, and small-scale expression in-house.

By providing clear guidance on which protein has the best chance of success from the start, eProtein Discovery reduces the time, cost, and uncertainty traditionally associated with protein expression and purification. Researchers can generate soluble, purified proteins, including challenging membrane proteins, for downstream functional testing in under 48 hours, significantly accelerating workflows compared with months-long cell-based methods. Founded in 2013, Nuclera has offices in Cambridge (UK) and Boston (US). For more information, please visit www.nuclera.com.

leadXpro is a specialist in membrane protein production and structure-based drug discovery, including GPCRs, ion channels and transporters. The company offers end-to-end capabilities spanning heterologous membrane protein expression, purification, biophysical characterization and high-resolution structure determination using cryo-electron microscopy and X-ray crystallography. leadXpro operates an advanced in-house cryo-EM facility and has unique proprietary access to major Swiss large-scale research infrastructures, including 3rd generation synchrotron (SLS) and X-ray free electron laser (SwissFEL), enabling rapid and precise determination of membrane protein–ligand structures and elucidating membrane protein-ligand interaction dynamics. For more information, please visit www.leadxpro.com.