New Database Revolutionizes Protein-Lipid Research

From combating cancer and infections to storing energy, lipid-protein interactions are critical to biological processes in cells. But the mechanisms that drive these interactions have historically been difficult to map and understand.

A study led by Georgia Tech is showcasing a new resource to help researchers understand the structure and function of these interactions — called assemblies — at both molecular and functional levels. The work is published in the Nature-family journal Communications Chemistry.

Called BioDolphin — short for Biological Database of Lipid-Protein Highly Inclusive Interactions — the resource is the first comprehensive, annotated database of protein-lipid interactions. Integrated into a user-friendly web server, BioDolphin is freely accessible to all. Users can easily view and download interaction data and systematically analyze lipid-protein assemblies.

“Understanding lipid-protein interactions is crucial in advancing our understanding of human health and disease treatment,” says the study’s corresponding author, Andrew McShan. “BioDolphin is the first resource to collect this type of information for all kinds of proteins, not just those found in membranes. And because it is publicly available, this information is now at the tips of researchers’ fingertips.”

“BioDolphin as a comprehensive database of lipid–protein binding interactions” is led by McShan, an assistant professor in the School of Chemistry and Biochemistry at Georgia Tech, alongside first author Li-Yen (Zoey) Yang, Bioinformatics Ph.D. student; School of Computational Science and Engineering Assistant Professor Yunan Luo; and Kaike Ping, a Ph.D. student at Virginia Tech.

Diving into accessible data

A curated database with richly annotated information, BioDolphin contains over 127,000 lipid-protein binding interactions. And while most databases of lipid-protein assemblies have focused solely on a specific type of protein — membrane proteins — BioDolphin expands beyond that.

“BioDolphin enables us to globally define the structural features of lipid-protein assemblies across the eight different classes of lipid compounds to understand their cellular function and roles in disease,” says McShan, adding that the database also provides information on paired lipid-protein annotation, experimental binding affinities, intermolecular interactions, and atomic structures across a wide range of lipid-protein interactions — all available to anyone with an internet connection.

A molecular blueprint for research — and teaching

“In the past, this research has been limited because lipids are notoriously difficult to study in the lab,” McShan says. "BioDolphin changes the paradigm. It is the first time that anyone has collected, annotated, and analyzed the known structural universe of lipid-protein interactions across all organisms.”

It’s a rapidly developing field. McShan was recently awarded a prestigious Curci grant for cutting-edge cancer research into lipid-based universal immunotherapies and vaccines.

Beyond research applications, the team hopes that BioDolphin will be a resource for biochemistry students. 

“The database can serve as a tool for teachers and students studying these protein-lipid interactions, which is often an underdeveloped topic in biology and biochemistry courses,” McShan says. “I hope that BioDolphin is a valuable resource for the researchers of today — and that it can also be a building block for the researchers of tomorrow.”

Funding: Shurl and Kay Curci Foundation, NSF Advanced Cyberinfrastructure Coordination Ecosystem: Services & Support (ACCESS) program, NIH National Institute of General Medical Sciences (NIGMS), Partnership for an Advanced Computing Environment (PACE) at the Georgia Institute of Technology, and Taiwan Ministry of Education Government Scholarship to Study Abroad program.

DOI: https://doi.org/10.1038/s42004-024-01384-z