DYNAMICS OF PROTEINS IN DIFFERENT SOLVENT SYSTEMS - ANALYSIS OF ESSENTIAL MOTION IN LIPASES

We have investigated the effect of different solvents on the dynamics of Rhizomucor miehei lipase. Molecular dynamics simulations were perfo rmed in water, methyl hexanoate, and cyclohexane. Analysis of the 400- ps trajectories showed that the solvent has a pronounced effect on the geometrical properties of the protein, The radius of gyration and tot al accessibility surface decrease in organic solvents, whereas the num ber of hydrogen bonds increases. The essential motions of the protein in different solvents can be described in a low-dimensional ''essentia l subspace,'' and the dynamic behavior in this subspace correlates wit h the polarity of the solvent, Methyl hexanoate, which is a substrate for R. miehei lipase, significantly increases the fluctuations in the active-site loop, During the simulation, a methyl hexanoate entered th e active-site groove, This observation provides insight into the possi ble docking mechanism of the substrate.