Korean researchers have developed a technology capable of precisely analyzing the structure of intrinsically disordered proteins (IDPs) at the atomic level—proteins known to cause intractable diseases such as dementia and Parkinson's disease but difficult to study due to their constantly changing forms.
According to the scientific community on the 1st, a research team led by Professors Yoo Woo-kyung of the Brain Science Department and Kim Jin-hae of the New Biology Department at DGIST announced they developed the innovative analytical technology through collaboration with a research team led by Dr. Lee Young-ho at the Protein Structure Drug Mechanism Research Group of the Korea Basic Science Institute (KBSI).
Approximately one-third of human proteins are IDPs—proteins that constantly change shape like tangled threads rather than maintaining fixed three-dimensional structures.
These proteins perform essential functions including intracellular signal transmission, but when abnormally modified or aggregated, they become key causes of neurodegenerative diseases such as Alzheimer's and Parkinson's, as well as metabolic disorders including type 2 diabetes. However, their highly dynamic nature has posed technical limitations in identifying specific modification mechanisms during various disease processes.
To overcome these limitations, the research team established an optimized fusion strategy combining computer simulation technology with actual experimental data. The team first generated tens of thousands of structural candidates that proteins could potentially form, utilizing artificial intelligence models, advanced simulations, and structural information from the Protein Data Bank (PDB).
They then applied the "maximum entropy" technique, which assigns higher weights to structures closest to actual protein states by comparing nuclear magnetic resonance (NMR) data obtained through experiments against these candidates. This technology has the advantage of accurately identifying intermediate-stage structures that proteins form for only brief moments.
The precise NMR experimental data provided by Dr. Lee Young-ho's research team at KBSI played a decisive role in this achievement. KBSI's precise NMR data, which can examine solution-state protein structures at the atomic level rather than solid or crystalline states, was critical in verifying whether the algorithm developed by the research team accurately reflects the physical properties of actual proteins and providing feedback. Through this, the team also succeeded in precisely tracking how protein structures change according to temperature or genetic mutations.
Professor Yoo stated, "This research is a valuable achievement resulting from the organic combination of DGIST's Supercomputing AI Education and Research Center's computational resources and advanced computational science technology with KBSI's world-class precision analysis infrastructure and analytical technology." He added, "By elucidating the structural secrets of intrinsically disordered proteins that were previously impossible to analyze, we expect this to become an important analytical tool for understanding the mechanisms of intractable diseases such as dementia and developing therapeutics to control them."
Dr. Lee said, "We plan to continue developing structural research tools targeting intrinsically disordered proteins and disease-related proteins through ongoing collaboration with DGIST." He added, "Together with the Korea Institute of Science and Technology Information, we will establish a 'Korean PDB' based on PDBj, one of the world's three major PDBs, to create a structural archive for intrinsically disordered proteins that lack fixed three-dimensional structures."
The research results were published on the 18th of last month in the Proceedings of the National Academy of Sciences (PNAS), a world-renowned scientific journal, and the study was conducted with support from the National Research Foundation of Korea (NRF) and KBSI.