Merz Group Research Featured on JACS Cover

“A molecular dynamics study of the zinc sensing transcriptional repressor Staphylococcus aureus CzrA was featured on the cover of the Feb 22nd edition of the Journal of the American Chemical Society. CzrA is a member of the ArsR/SmtB family of metal sensor proteins and functions through a mechanism of allosteric negative regulation. The cover shows the protein undergoing a quaternary structural switch from a “closed” DNA-bound conformation to a more “open” conformation in response to Zn(II) binding. This disrupts the DNA-binding interface and reduces the binding affinity of CzrA for DNA and, ultimately, transcriptional de-repression. In collaboration with the Giedroc group at the University of Indiana, the Merz group used classical MD, QM/MM and QM/MM MD methods to investigate the molecular basis for the large conformational motions and the allosteric coupling free energy (~6 kcal/mol) associated with metal ion binding.”