The use of the MM3* and ESFF force fields in conformational analysis of carbohydrate molecules in solution: The methyl alpha-lactoside case.

The solution conformation of methyl alpha-lactoside has been studied through NMR spectroscopy and molecular mechanics calculations using the MM3* and ESFF force fields. The steady-state and transient NOEs have been interpreted in terms of an ensemble average distribution of conformers, making use of the complete relaxation matrix approach. The molecular mechanics calculations have been performed at two dielectric constants (epsilon = 1 and 80 Debyes) for both force fields in an exhaustive way, and in the case of MM3* have been complemented with calculations using the continuum solvent model GB/SA. Relaxed energy maps and adiabatic surfaces have been generated for the different dielectric constants, The probability distribution of conformers has been estimated from these steric energy maps. MM3* molecular dynamics simulations in vacuo and with GB/SA have also been performed. The comparison between predicted and experimental results indicate that the beta-(1- > 4) glycosidic linkage shows some fluctuations among three low-energy regions, although it spends ca. 90% of its time in the region close to the global minimum. The results indicate that MM3*, when used with high dielectric constants or with the GB/SA solvent model, satisfactorily reproduces the conformational properties of methyl alpha-lactoside in water solution. The use of ESFF only provides a qualitative agreement between experimental and theoretical results. (C) 1997 Elsevier Science B.V.