CONFORMATIONAL-ANALYSIS OF METHYL 6-O-[(R)-1-CARBOXYETHYL]-ALPHA-D-GALACTOPYRANOSIDE AND 6-O-[(S)-1-CARBOXYETHYL]-ALPHA-D-GALACTOPYRANOSIDEBY MM AND LANGEVIN DYNAMICS SIMULATIONS

The conformational space of methyl 6-O-[(R)- and (S)-1-carboxyethyl]-a lpha-D-galactopyranoside has been investigated. A grid search employin g energy minimization at each grid point over the three major degrees of freedom, namely phi, psi and omega, identified low energy regions. The R-isomer shows five low energy conformers within ca. 1 kcal mol(-1 ) of the global energy minimum. The S-isomer has two conformers within a few tenths of a kcal mol(-1) of the global energy minimum. Langevin dynamics simulations have been have been performed at 300 K for 30 ns of each isomer. The phi dihedral angle has as its major conformer (g- ) for the R-isomer whereas it is the (g+) conformer for the S-isomer. For the omega dihedral angle the (t) conformer has the highest populat ion for both isomers. The dihedral angle omega has the (g+) conformer most highly populated, both for the R-and S-isomer. The above five and two conformational states for the R-and S-isomers, respectively, make up 90% in each case of the populated states during the Langevin dynam ics (LD) simulations. Rate constants for the omega dihedral angle have been calculated based on a number correlation function. Three bond ho mo-and heteronuclear, i. e. proton and carbon-13, coupling constants h ave been calculated from the dynamics trajectories for comparison to e xperimental values. The heteronuclear coupling constant H2', C6 has be en measured for the S-isomer and found to be 3.3 Hz. The J value calcu lated from the LD simulations, namely 2.6 Hz, is in fair agreement wit h experiment. A comparison to the X-ray structure of the R-isomer show s that the conformation of the crystalline compound occupies the low e nergy region most highly populated as a single R-conformer (30%) durin g the LD simulations.