Molecular dynamics simulations of the plant-specific insert monomer at pH 7.4

This study examines the underlying mechanics driving tertiary structure and quaternary conformational changes in silico of the saposin-like domain, the plant-specific insert, of a potato (Solanum tuberosum) aspartic protease as a function of pH. Umbrella sampling was used to determine the free energy change of dissociation of the plant-specific insert at acidic and neutral pH and revealed that a lower barrier to dissociation exists at neutral pH as compared to acidic pH. Furthermore, principal component analysis was used to characterize tertiary structure conformational changes at active (pH4.5)and neutral pH of monomeric plant-specific insert. The results indicate that the plant-specific insert may adopt a tertiary structure similar to the characteristic saposin-fold at neutral pH and suggests a potential new structural motif among saposin-like proteins at pH 4.5.