AWSEM-predicted archaeal histone heterodimer follows the same folding mechanism.

Previous biochemical studies demonstrate the formation of archaeal heterodimers HMfA/HMfB in vitro, which, however, was not structurally characterized. Based on our finding of eukaryotic histones (Fig 2), we hypothesize that archaeal histone heterodimers adopt a structure and binding-folding mechanism analogous to other eukaryotic histone dimers. We took HMfA and HMfB monomer structures from their homodimer complexes (PDB: 1B67 and 1A7W), and predicted their heterodimer structure using simulated annealing. We further applied umbrella sampling and calculated its free energy profiles. (A) Q value of the archaeal histone HMfA (blue) and HMfB (green), and its dimer (magenta) during the simulated annealing and the final prediction of archaeal heterodimer HMfA/HMfB structure are shown. (B) Free energy profile calculated at 300 K are projected on Qmonomer and the α2—α2 angle (left), and radius of gyration Rg and the α2—α2 angle (right). (TIF)