SBIR Phase I: A physics-based machine learning platform for crystal structure prediction of small drug molecules

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The broader impact of this Small Business Innovation Research (SBIR) Phase I project is to accelerate and reduce the cost of the early stages of small molecule pharmaceutical research. The number of drugs a pharmaceutical company can bring to market is limited by the time, cost, and complexity involved in developing each drug. The research and development process typically takes around 10 years, and few drugs make it onto the market each year. This technology may be especially impactful in improving the frequency at which small molecule drugs are developed for understudied diseases, which collectively impact over 30 million Americans. By reducing the cost and time to market for new pharmaceuticals, the project could advance the industry and bring life-changing therapeutics to underserved people who are suffering from illnesses where there are presently no drug options.This project develops technologies to solve the crystal structure prediction (CSP) problem. The crystalline structure of small molecules and peptides determines many pharmacological characteristics including solubility, oral bioavailability, shelf-life stability, and toxicity. Experimental determination of the crystal structure is expensive and requires significant human labor to conduct, so a computational approach would reinvent the characterization of small molecule drugs. The proposed technical innovation combines a novel energy prediction models based on quantum chemistry with a machine learning method for efficiently sampling the vast space of possible crystal structures. The resulting technology will help pharmaceutical companies de-risk their drug development process by allowing them to analyze crystal structures computationally before having to synthesize them in the lab.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.