MOLECULAR-DYNAMICS SIMULATIONS OF AN ENZYME SURROUNDED BY VACUUM, WATER, OR A HYDROPHOBIC SOLVENT

We report on molecular dynamics simulations of a medium-sized protein, a lipase from Rhizomucor miehei, in vacuum, in water, and in a nonpol ar solvent, methyl hexanoate. Depending on force field and solvent, th e molecular dynamics structures obtained as averages over 150 ps had r oot-mean-square deviations in the range of 1.9 to 3.6 Angstrom from th e crystal structure. The largest differences between the structures we re in hydrogen bonding and exposed surface areas of the protein. The s urface area increased in both solvents and became smaller in vacuum. T he change of surface exposure varied greatly between different residue s and occurred in accordance with the hydrophobicity of the residue an d the nature of the solvent. The fluctuations of the atoms were larges t in the external loops and agreed well with crystallographic temperat ure factors. Root-mean-square fluctuations were significantly smaller in the nonpolar solvents than they were in water, which is in accordan ce with the notion that proteins become more rigid in nonpolar solvent s. In methyl hexanoate a partial opening of the lid covering the activ e site occurred, letting a methyl hexanoate molecule approach the acti ve site.