Ana M. Melo, a professor and researcher at Instituto Superior Técnico, affiliated with the Institute for Bioengineering and Biosciences (iBB) and the Associate Laboratory i4HB, is one of the authors of an article published in Nature Methods that proposes a new strategy for better understanding intrinsically disordered proteins.
The researcher is the only author with a Portuguese affiliation in this study titled “Toward a unified framework for determining conformational ensembles of disordered proteins”, whose contribution focused on single-molecule FRET (smFRET), which is unique in Portugal.
The single-molecule FRET technique allows us to observe how individual protein molecules change shape in real time. These measurements provide crucial information about the range of structures that disordered proteins can adopt. The paper, co-authored by Ana M. Melo, establishes an integrated approach to studying intrinsically disordered proteins (IDPs), a class of proteins that do not adopt a single stable structure but instead constantly change conformations.
Unlike globular proteins, which adopt stable and well-defined structures, these proteins are flexible in nature, which poses “fundamental challenges to structural biology”. The researcher explains that, through the successive combination of different experimental techniques, the new study proposes “a unified conceptual framework” that allows these proteins to be described in a more realistic and integrated way.
Thus, the work carried out at iBB and i4HB utilises smFRET, a high-resolution technique, enabling the collection of fundamental data for the “direct observation of structural fluctuations at the level of individual molecules”, which is essential for refining and validating computational models.
For Ana M. Melo, this research carried out at Técnico is of “particular significance” as it provides “unique experimental data that captures the heterogeneity and dynamics of these proteins with a level of detail that is difficult to achieve using other methods”.
The researcher emphasises that this study represents a “significant advance in the field” by complementing recent progress in structural prediction and by opening up “new perspectives for understanding the role of these proteins at the cellular level and in various diseases, such as cancer and neurodegenerative diseases”. Additionally, the study may contribute to the development of “molecular intervention strategies”, particularly to “identify new therapeutic targets and the rational design of drugs targeting intrinsically disordered proteins”.
This work is expected to represent a “significant advance” in the integration of experimental data and computational models, enabling, with the support of artificial intelligence, a more precise description of the dynamic conformations of IDPs in the coming years.
The researcher also believes that the availability of single-molecule FRET instrumentation positions Técnico as “a leading European institute in this field”. To strengthen the collaborative network and consolidate Técnico’s position as an international leader, she recently organised a COST meeting in Lisbon that brought together leading international researchers in the fields of smFRET and computational simulation.
