Fig. 2.

Structure prediction. (A) fd-coat protein. (Left) Backbone superposition of the experimental structure determined by solid-state NMR (19) (blue) and the lowest-energy decoy generated by ROSETTA (pink) starting from an extended chain. The rmsd over 30 C^α atoms is 2.4 Å. (Right) All-atom representation of the lowest-energy decoy generated by ROSETTA. The boundaries predicted by ROSETTA between the hydrophobic core and the interface regions of the membrane are represented with a black solid line. (B) Glycophorin A. Isolated monomers were docked with the ROSETTA protein–protein docking protocol and the all-atom membrane force field. The superposition between the native (blue) and the lowest-energy predicted structure (pink) is represented. The rmsd over 45 C^α atoms is 0.65 Å. (C and D) Ab initio structure prediction of polytopic membrane proteins. Native polytopic membrane protein conformations define a narrow energy basin in the all-atom conformational energy landscape. When near-native topologies are generated at the coarse-grained level, all-atom relaxed decoys define a funnel toward the native basin and the lowest-energy predicted structures have near-atomic resolution structures. In the energy versus rmsd plots, nonnative (red points) (generated from sequence by the ROSETTA coarse-grained structure prediction mode) and native conformations (green points) were relaxed by sampling the conformational degrees of freedom of all backbone and side-chain atoms. Cartoons show superposition between the native (blue) and the lowest-energy predicted structure (pink). Boxed areas show regions where close to native side-chain packing arrangements were obtained. The rmsd values are 2.1 Å over 111 C^α atoms for BRD4 (C) and 2.4 Å over 139 C^α atoms for VATP (D).