[Molecular dynamics analysis of chymosin conformations in solution and in crystalline environment]

The method of molecular dynamics in explicit solvent was applied to test the hypothesis of the existence of a self-inhibited form of chymosin in solution. The paths and energies were calculated for chymosin in solution and in a crystalline environment. The modeling revealed that the intermolecular contacts of chymosin in crystal have negligible influence on the energy stabilization of its self-inhibited conformation. On the other hand, upon molecular dynamics simulation of the active and self-inhibited forms in solution their conformational energies proved to be quite close and the potential barrier between them relatively low. All this supports the possibility of chymosin to adopt spontaneously the self-inhibited conformation in solution, and indicates that it is one of the really existing enzyme forms rather than a crystal packing artifact. The results obtained open novel approaches to studying the specificity of chymosin as well as other aspartic proteinases.