Deep-tech project LIGATE is harnessing the revolutionary power of exascale computing together with advances in AI, big data analytics and simulation software to boost Exscalate’s drug discovery platform in identifying effective drugs to tackle unmet medical needs

There are more than 10,000 diseases effecting humans and only 500 approved treatments. This proves there is a lot of drug discovery yet to do to tackle the unmet medical needs of patients. The challenge is that it can take many years for a new drug to progress from the early discovery of compounds to clinical trials and regulatory approval. Even then only 1 in 5,000 drugs actually makes it to market as the success rate is so low with very few progressing past clinical trials. This results in a very lengthy and costly drug discovery process. 

To address this problem a public-private consortium of ten European partners were brought together in the LIGATE project. The aim is to develop a portable and tunable drug discovery platform that leverages the unprecedented availability of European HPC resources together with advances in technology - including artificial intelligence, big-data analytics, virtual screening software and virtualization - to support the scientific community in finding novel solutions to worldwide public health crises, such as pandemics.

Coordinated by Exscalate, this three-year project will run until 31 December 2023 and is supported by the European Commission and co-funded by the European High-Performance Computing Joint Undertaking. The project will further boost the Exscalate platform to offer the highest accuracy, quality, efficiency, scalability and portability. 

LIGATE will support cross-disciplinary workflows in drug design and development. Unlike current systems, it is able to consider all the complexity and systemic perturbations a disease produces. This predictability, together with the full solution automation and the availability of the exascale computing systems, will enable a full in silico drug discovery campaign to be run in less than one day. Importantly, this state-of-the-art tool will enable scientists to rapidly test hypothesis.

In terms of the portability and efficiency of the platform, the evolution of HPC architectures is heading toward specialization and extreme heterogeneity, including future exascale architectures. As such, the LIGATE solution will also focus on code portability. This means that the Computer Aided Drug Design (CADD) platform will be designed to be hardware architecture independent enabling the solution to leverage all HPC centers in Europe.  

The ultimate goal of the LIGATE project is to implement an integrated platform for the design of novel drugs that utilizes the extreme speed of Exscalate’s LiGen molecular docking tool (> 2K mol/Sec/GPU), which is able to scan trillions of molecules in hours instead of years to offer the most accurate results.  The development of exascale-ready architecture will also allow users to study the pharmacological activity of compounds on multiple targets unlocking the potential use of in silico quantitative system pharmacology models to support the mechanistic understanding of biological and pathological systems, and so fully embracing the real complexity of biological systems. LIGATE will also help reduce animal testing as the platform allows for more accurate target driven models of toxicity .

Harnessing the power of these advanced technologies to boost the drug discovery process is vital, as has been seen in recent pandemics, including Zika and Covid-19. Exscalate was involved in two public-private consortia that were involved in identifying drugs to fight these pandemics. ANTAREX4ZIKA, which identified a potent inhibitor for the Zika virus, and EXSCALATE4CoV, which validated the osteoporosis drug Raloxifene as an effective treatment for inflammatory processes induced by COVID-19. 

The LIGATE project builds on the results of these projects and will soon launch the first release of its integrated CADD platform. The platform is already supporting several research groups at academic institutions and biotech companies across Europe.

The first application of LIGATE will be in the identification of novel broad spectrum antiviral drugs evaluating trillions of molecules versus viral functional targets (helicase, polymerase, protease, etc). The best compounds will then be experimentally validated in antiviral tests and with Xray or cry-EM methods.

At the end of the project, the consortium partners will make the platform available free of charge to the scientific community as a cloud application with the hope that it will be used to support the discovery of novel treatments in the fight against viral pandemics and multidrug-resistant bacteria.

More information and project updates: www.ligateproject.eu.