The mechanism by which cells deactivate their switches has been discovered

The research, coordinated by scholars Angela Parise and Alessandra Magistrato and published in the Journal of the American Chemical Society, analyzed these real molecular switches whose alterations are linked to the development of various pathologies, including tumor formations and metastases. Through advanced computational simulations integrating classical molecular dynamics and quantum methods, the team observed at the atomic level the transition of the RhoA protein from active to inactive configuration.

Angela Parise, first author of the study commented: “The study has identified a mechanism previously unknown. During the reaction, a glutamine, an amino acid present in the active site of the protein, temporarily changes its structure, behaving like a sort of shuttle that transfers protons and makes the chemical reaction possible. At the end of the process, the entry of water molecules allows the protein to return to its initial configuration, ready for a new cycle of activity. This model resolves a debate that has been open for years on the functioning of Rho GTPase“.

The direct observation of atomic steps opens up new perspectives for understanding molecular processes and for the design of future therapeutic interventions. As research director Alessandra Magistrato specifies: “The possibility of following the movement of the atoms during the reaction has allowed us to understand how the protein is able to deactivate itself and become ready for a new cycle. This is an approach that can also be applied to the study of many other proteins involved in the regulation of cellular functions“, confirming the role of computational methodologies in the study of pathological processes and pharmacological strategies.