Molecular Modelling Studies of Bovine and Camel Chymosin-κ-Casein Complexes

Abstract

We present computational studies of two homologous mammalian aspartic proteases (calf and camel chymosin) complexed with 16-residue fragments of their native peptide ligands (cow and camel κ-casein) and the cross-complexes. Using molecular docking calculations, homology modelling and molecular dynamics simulations, we compare the binding modes of the four systems. The complexes are of industrial interest because camel chymosin has recently been marketed as an alternative to bovine chymosin as an enzyme to clot milk in cheese manufacturing. The camel enzyme has been shown to have 70% higher clotting activity and only 20% of the unspecific protease activity for bovine κ-casein as compared to the bovine enzyme. Interestingly, bovine chymosin has a very low proteolytic rate for camel κ-casein. The models provide putative atomic coordinates for these complexes, for which there are no available crystallographic or NMR structures, and help to explain some existing experimental results.View Large Image | View Hi-Res Image | Download PowerPoint Slide