Project Grant R35GM166357

The National Institute of General Medical Sciences awarded Scripps Research Institute $506,000 on July 20, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to decode membrane protein folding and functional principles using designed building blocks.

The research integrates protein design with biophysical experiments to clarify fundamental chemical rules and sequence-structure relationships governing how proteins interact in lipid membranes. Membrane proteins are major drug targets but remain complex, dynamic, unstable, and difficult to study; current technical and knowledge gaps limit understanding of how these proteins behave in heterogeneous lipid environments. The program aims to develop novel strategies for illuminating generalizable first principles and software describing how stability, selectivity, and function can be encoded in transmembrane spans. The research pursues three distinct directions via a common approach: building synthetic membrane proteins as simplified model molecules to test data-driven hypotheses for how transmembrane regions assemble and shape their lipid surroundings. The first project capitalizes on the paradigm that membrane domains pack their transmembrane helices using a limited basis set of core geometries reused across protein folds; the program hypothesizes that defining sequence patterns and molecular features encoding these fundamental transmembrane building blocks will establish biophysical rules explaining most protein interactions in lipid.

The award covers the period of performance from July 20, 2026, through April 30, 2031, with work performed in La Jolla, California.