CNIO researchers have used the German supercomputer SuperMUC, the 6th fastest supercomputer in the world, to study structural changes of EGFR mutants and their oncogenic potential
Spanish National Cancer Research Centre (CNIO) researchers have used computational simulations to uncover why tiny mutations in EGFR -epidermal growth factor receptor- can trigger structural and functional changes in the protein associated with certain types of brain and lung cancer. These findings were published this week in the journal Proceedings of the National Academy of Sciences (PNAS).
To date, studies have shown that certain EGFR mutations cause cellular aberrations that may eventually contribute to cancer. By using the SuperMUC German supercomputer, researchers Francesco Luigi Gervasio, head of the Computational Biophysics Group at the CNIO, and Ludovico Sutto, a member of his team, investigated changes in the shape of EGFR mutant proteins over a small range of timescales, ranging from nanoseconds to milliseconds. The results reveal how these small chemical changes in the mutant proteins make them adopt profoundly different shapes that dramatically affect their properties and turn them into active, cancer-causing versions.
“Understanding why and how small changes in the protein’s makeup can dramatically change their behaviour is a crucial question, as it would explain why these proteins can become potent triggers for cancer”, says Gervasio.
Effects of oncogenic mutations on the conformational free-energy landscape of EGFR kinase. Sutto L, Gervasio FL. PNAS (2013). doi: 10.1073/pnas.1221953110