The gingipains are cell surface expressed, cysteine proteases with broad substrate specificity and are major virulence factors of the pathogen Porphyromonas gingivalis. An earlier molecular biology study of wild-type RgpB, an arginine-specific gingipain, and a number of mutants suggested that residues in the C-terminal region played a critical role in the export of protein.
We report the results of a series of ‘solvated’ molecular dynamics simulations of both the wild-type sequence and the mutated sequences performed using the amber7_ff02 force field.
The wild-type sequence folds rapidly (~ 1 ns of simulation time) to an a-helical structure. Folding is temperature dependent with the helical structure partially unfolded at lower simulated temperatures - consistent with an entropically driven process. The mutant sequences are also capable of forming stable a-helical structures. However, mutations that prevent protein export are found to alter either the amount or the distribution of hydrophobic surface associated with the a-helix.
The results are consistent with the C-terminal motif being a fold-nucleation site that plays a critical role in forming the secondary structure of these proteins.