查看文章

We describe the application of our recently proposed method of hierarchical optimization of the protein energy landscape to optimize our off-lattice united-residue (UNRES) force field using single training proteins. First, the IgG-binding domain from streptococcal protein G (PDB code 1IGD) was treated; earlier attempts to use this protein to optimize the force field by optimizing the energy gap and Z score between the nativelike and non-native structures failed. The structure of this protein consists of an N-terminal antiparallel β-hairpin, a middle α-helix, and a C-terminal antiparallel β-hairpin, these elements being referred to as β₁, α₂, and β₃, respectively, with the two hairpins forming a parallel β-sheet packed against the α-helix. In our earlier study, one of these elements was assumed to form at level 1, two at level 2, and three at level 3, and higher levels corresponded to the proper packing of two or more elements …