Mechanics and dynamics of B1 domain of protein G: Role of packing and surface hydrophobic residues

The structural organization of the B1 domain of streptococcal protein G (PG A) has been probed using molecular dynamics simulations, with a particular emphasis on the role of the solvent exposed Ile6 residue. In addition to th e native protein (WT-PGA), three single-mutants (16G-PGA, I6F-PGA, and I6T- PGA), one double-mutant (I6T,T53G-PGA), and three isolated peptide fragment s (corresponding to the helix and the two beta-hairpins) were studied in th e presence of explicit water molecules. Comparative analysis of the various systems showed that the level of perturbation was directly related to the hydrophobicity and the size of the side chain of residue 6, the internal ri gidity of the proteins decreasing in the order I6T-PGA > I6G-PGA > WT-PGA > IGF-PGA. The results emphasized the importance of residue 6 in controlling both the integrity of the sheet's surface and the orientation of the helix in relation to the sheet by modulation of surface/core interactions. The e ffects of mutations were delocalized across the structure, and glycine resi dues, in particular, absorbed most of the introduced strain. A qualitative structural decomposition of the native fold into elementary building-blocks was achieved using principal component analysis and mechanical response ma trices. Within this framework, internal motions of the protein were describ ed as coordinated articulations of these structural units, mutations affect ing mostly the amplitude of the motions rather than the structure/location of the building-blocks. Analysis of the isolated peptidic fragments suggest ed that packing did not play a determinant role in defining the elementary building-blocks, but that chain topology was mostly responsible.