Open state conformation of NS2B generated using GPS-Rosetta.

<p>(A) Scatter plot of 5,000 all-atom structures showing their combined score of weighted PCS + Rosetta energy versus the Cα RMSD of NS2B in the homology model built on the crystal structure 2FOM of the open conformation. The final selected structure (red point) has the lowest combined energy score and is referred to as the “open GPS-Rosetta structure”. The four next-lowest combined score structures are represented by blue points. (B) Superimposition of the best GPS-Rosetta structures onto the homology model. The open GPS-Rosetta structure is shown in red (NS2B) and grey (NS3pro) and the homology model in green (NS2B) and grey (NS3pro). The Cα RMSD of NS2B in the open GPS-Rosetta model is 2.7 Å relative to the homology model. The NS2B segments of the next four lowest-energy structures have RMSDs ranging from 2.7 to 3.1 Å and are displayed in different shades of blue. The superimposition shown in the figure used the Cα atoms of NS2B only. (C) Same as (A), except that scoring used PCSs only. (D) Same as (B), except using the structures with the lowest PCS scores identified in (C). In all five models, NS2B has a Cα RMSD between 2.7 and 3.6 Å relative to the NS2B part in the homology model.