Phosphate Uptake and Interactions in the PhoX protein

GENERAL, IGNACIO J.

Sao Paulo

Workshop; Workshop of Molecular Modelling in Drug Discovery and Design (WMMD3); 2022

Universidade Federal do ABC

PhoX is a phosphate binding protein, present in the plant pathogenicbacterium Xanthomonas citri. Although its function is being activelystudied, not much is known about the molecular mechanisms that drive itsinteraction with phosphate ions. In this work, we use computational techniques,such as Elastic Network Models and Molecular Dynamics, to investigate theprotein’s structural changes and dynamics, with a focus on the molecular levelaspects that govern the interactions of PhoX with phosphate ions. We found thatunbound PhoX has a tendency to explore the closed conformation, wheretwo mayor domains of the protein become close to each other, but they reach alocked and stable state only in the presence of PO4, which acts as a glue(via salt-bridges) between the domains. This closed conformation was used asthe starting point of a binding free energy calculation of PhoX/PO4, whichcoincided with a previous experimental result, supporting our model.