Proline isomerization effects in the amyloidogenic protein β2-microglobulin

Maria Celeste Maschio, Jacopo Fregoni, Carla Molteni, Stefano Corni

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)
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The protein β2-microglobulin (β2-m) can aggregate in insoluble amyloid fibrils, which deposit in the skeletal muscle system of patients undergoing long-term haemodialysis. The molecular mechanisms of such amyloidogenesis are still not fully understood. A potential, although debated, triggering factor is the cis to trans isomerization of a specific proline (Pro32) in β2-m. Here we investigate this process in the native protein and in the aggregation-prone mutant D76N by means of molecular dynamics and the enhanced sampling method metadynamics. Our simulations, including the estimation of the free energy difference between the cis and trans isomers, are in good agreement with in vitro experiments and highlight the importance of the hydrogen bond and hydrophobic interaction network around the critical Pro32 in stabilizing and de-stabilizing the two isomers.

Original languageEnglish
Pages (from-to)356-367
Number of pages12
JournalPhysical Chemistry Chemical Physics
Issue number1
Publication statusPublished - 6 Jan 2021


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