RESTRAINED MOLECULAR-DYNAMICS STUDY OF THE INTERACTION BETWEEN BOVINE KAPPA-CASEIN PEPTIDE-98-111 AND BOVINE CHYMOSIN AND PORCINE PEPSIN

The cleavage of bovine kappa-casein at the Phe(105)-Met(106)* bond by chymosin or pepsin is the first stage in casein micelle coagulation and casein digestion. The nature of the interaction of the peptide His(98)-Pro-His-Pro-His-Leu-Ser-Phe(105)- Met-Ala-Ile-Pro-Pro-Lys(111) with chymosin and porcine pepsin was investigated using molecular modelling and energy minimization techniques. This study verified and extended a proposed model that electrostatic binding (involving His(98), His(100), His(102) and Lys(111) or Lys(112)) at either end of the active site cleft of chymosin is important for the positioning of residues 103-108 in the cleft. The peptide conformation remained unchanged in going from solution to binding into the active site cleft, with the exception that optimum binding of substrate to chymosin required the isomerization of the His(98)-Pro(99) peptide bond from the trans to the cis conformation. The study also identified an acidic region in porcine pepsin that is in a position to form strong electrostatic, interactions with the histidines at the N-terminus of the peptide.