Invited Talk by G. Volpe at the TR+ Conference 2026: From Static to Dynamics, LINXS, Lund, 21 September 2026

Conceptual models of protein folding: funnel versus foldon. (Figure from the Authors of the manuscript.).

How do proteins fold?
Date: 21 September 2026
Time: 13:15
Place: LINXS at The Loop, Lund

Giovanni Volpe will give the invited talk “How do proteins fold?” at the TR+ Conference 2026: From Static to Dynamics, organized by LINXS and MAX IV in Lund from 21 to 23 September 2026. The conference brings together researchers working on time-resolved methods to investigate the structural and functional dynamics of biomolecules.

How proteins fold remains a central unsolved problem in biology. While the idea of a folding code embedded in the amino acid sequence was introduced more than six decades ago, this code remains undefined. Although we now have powerful predictive tools to predict the final native structure of proteins, we still lack a predictive framework for how sequences dictate folding pathways.

Two main conceptual models dominate as explanations of folding mechanism: the funnel model, in which folding proceeds through many alternative routes on a rugged, hyperdimensional energy landscape; and the foldon model, which proposes a hierarchical sequence of discrete intermediates.

Recent advances on two fronts are now enabling folding studies in unprecedented ways. Powerful experimental approaches—in particular, single-molecule force spectroscopy and hydrogen–deuterium exchange assays—allow time-resolved tracking of the folding process at high resolution. At the same time, computational breakthroughs culminating in algorithms such as AlphaFold have revolutionized static structure prediction, opening opportunities to extend machine learning toward dynamics.

Together, these developments mark a turning point: for the first time, we are positioned to resolve how proteins fold, why they misfold, and how this knowledge can be harnessed for biology and medicine.

Reference: Bustamante, C., Kaiser, C. M., Lindahl, E., Sosa, R., & Volpe, G. (2026). “How proteins fold.” Nature Reviews Molecular Cell Biology. Advance online publication.

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