THEORETICAL-STUDIES OF RHIZOMUCOR-MIEHEI LIPASE ACTIVATION

Computational methods have been used to study the extensive conformati onal change of Rhizomucor miehei lipase upon activation. The present s tudy considers the possible activation route, the energies involved an d molecular interactions during the conformational change of the lipas e in a hydrophobic environment. The conformational change was studied by conventional molecular dynamics methods and with a combined molecul ar dynamics and mechanics protocol, in which the conformational change was simulated by restraining Calpha pseudotorsional angles in small s teps between the two crystallographically observed positions of the li d. In the closed conformer of the enzyme the active site is completely buried under a short helical loop, 'the lid'. The activation of the l ipase consists of a movement of the lid, which results in an open conf ormer with an exposed active site. From the results of the simulations in the present work we suggest that the lipase in a hydrophobic envir onment is stabilized in the open form by electrostatic interactions.