What if one of biology’s most fundamental rules no longer holds?
For decades, we’ve understood proteins through a simple logic: sequence → structure → function.
But not all proteins follow the rules.
A new study published in Nature Methods challenges this view by focusing on intrinsically disordered proteins (IDPs), proteins that don’t settle into a single structure, but constantly shift between many. Elusive, dynamic and deeply involved in processes like cell regulation, cancer, and neurodegenerative diseases.
The work, “Towards a Unified Framework for Determining Conformational Ensembles of Disordered Proteins,” brings together researchers from Europe and the US, including Ana M. Melo affiliated with Institute for Bioengineering and Biosciences
Ana Melo applies single-molecule FRET (smFRET), a technique that tracks how individual protein molecules change shape in real time. Not averages. Not snapshots. But motion, as it happens. This capability is rare. The smFRET instrumentation available at Técnico is unique in Portugal, placing it among a small number of laboratories in Europe able to probe protein dynamics at this level.
By combining experimental approaches like smFRET with computational modelling, the study proposes a unified way to describe these constantly shifting proteins.
Because when structure is no longer fixed, biology becomes less predictable.
And understanding that complexity is where the next breakthroughs will come from.