Active Site Studies\nto Explain Kinetics of Lipases\nin Organic Solvents Using Molecular Dynamics Simulations

This study investigates the intricate dynamics underlying\nlipase\nperformance in organic solvents using comprehensive molecular dynamics\n(MD) simulations, supported by enzyme kinetics data. The study reveals\nthat a single criterion can neither predict nor explain lipase activity\nin organic solvents, indicating the need for a comprehensive approach.\nThree lipases were included in this study: <i>Candida antarctica</i> lipase B (CALB), <i>Rhizomucor miehei</i> lipase (RML),\nand <i>Thermomyces lanuginosus</i> lipase (TLL). The lipases\nwere investigated in acetonitrile, methyl <i>tert</i>-butyl\nether, and hexane with increasing water activity. Computational investigations\nreveal that CALB’s activity is negatively correlated to water\ncluster formations on its surface. In contrast, TLL’s and RML’s\nactivity profiles show no negative effects of high water activity.\nHowever, TLL’s and RML’s activities are highly correlated\nto the conformation and stability of their active site regions. This\nstudy may pave the way for tailored applications of lipases, highlighting\nsome of the factors that should be considered when lipase-catalyzed\nreactions are designed.