MOLECULAR-DYNAMICS SIMULATIONS OF MALTOSE IN WATER

The conformational preferences and flexibility of oc-maltose were calc ulated using a modified GROMOS potential energy function. Six molecula r dynamics (MD) simulations of cu-maltose with explicit inclusion of w ater were run for up to 1000 ps each, starting from different conforma tions of the glycosidic linkage, the hydroxymethyl groups, and the hyd roxyl groups. Comparison of calculated ensemble-averaged optical rotat ions with experimental data demonstrated an excellent agreement. Reaso nable agreement was also found between experimental and calculated tim e-averaged NMR parameters. The global minimum centered at phi/psi(3) = -49 degrees/-36 degrees was populated to more than 90% of the time. T he second minimum with approximate to 11 kJ/mol higher potential energ y at phi/psi = -29 degrees/-173 degrees represented the inverted confo rmation. Transitions between both minimum regions were only found from the local into the global minimum within the total simulation time of 5400 ps. The overall ratio between the staggered populations of the h ydroxymethyl groups is gg:gt:tg = 70:23:6 for the reducing glucose, an d gg:gt:tg = 55:38:6 for the nonreducing residue. Average lifetimes of the rotamers of the hydroxymethyl groups range between 5 ps for tg an d 700 ps for gg conformers. The lowest energy barriers between the rot americ populations were estimated to be between 12 kJ/mol and 16 kJ/mo l. Cluster analysis techniques employed to analyze the large amount of data in multidimensional space revealed correlations between the glyc osidic linkage and the staggered forms of the hydroxymethyl groups. In terresidue hydrogen bonds that were found in less than 5% of all confo rmations occurred when the glycosidic linkage adopted conformations wi th relatively high phi and psi values. Several additional minima that had been found from in vacuo studies are not stable once water is incl uded since the importance of intramolecular hydrogen bonds is drastica lly reduced. Methodological aspects and the efficiency of MD simulatio ns for reaching conformational equilibria are discussed.