Federal Grant Award Summary

The National Institute of General Medical Sciences (NIGMS) awarded Lawrence Berkeley National Laboratory $662,335 under the Biomedical Research and Research Training program (CFDA 93.859) for a five-year project period from July 1, 2026, through June 30, 2031. This Project Grant supports fundamental research enabling time-resolved studies of small molecule-protein interactions with pharmacological relevance using serial crystallography techniques. The research leverages recent advances in X-ray free electron laser (XFEL) technology and synchrotron radiation (SR) crystallography to conduct structural studies at room temperature under near-physiological conditions, moving beyond traditional frozen-sample approaches to capture real-time protein dynamics and binding mechanisms.

The primary deliverables include development of robust methodologies for introducing biological samples into X-ray interaction regions in a continuous manner to minimize sample consumption, given the "probe before destroy" approach inherent to XFEL studies. Additionally, the project aims to generate molecular-level insights into protein-ligand interactions for compounds with pharmacological importance, with emphasis on developing fast, efficient, and homogeneous mixing techniques to produce dynamic structural data. The research conducted at Berkeley, California will advance understanding of enzymatic reaction mechanisms and ligand binding behavior, with outcomes applicable to multiple biomedical research domains supported by NIGMS's mission to increase understanding of biological processes foundational to disease diagnosis, treatment, and prevention.