A comparison of the geometry and of the energy results obtained by application of different molecular mechanics force fields to methyl α-lactoside and the C-analogue of lactose

Abstract

The applicability of a number of standard molecular mechanics force fields, namely AMBER/Homans, CVFF, CFF91, ESFF, and MM3 ∗, and of the AMI semiempirical Hamiltonian, to the molecular modelling of methyl α-lactoside is described. A protocol based on the calculation of relaxed energy maps for a significant number of initial structures has been employed. Different dielectric constants, as well as a continuum model solvent have been used. The geometric characteristics (distances and torsion and valence angles) of the low energy minima have been gathered and compared to experimental solution NMR and solid state X-ray data. Concerning the energies, the relative steric energy values provided by the different programs have been translated into ensemble average distributions of conformers which, in turn, have been employed to generate NMR parameters, i.e. NOE, NOESY, and ROESY intensities and homo- and hetero-nuclear coupling constants. The results indicate that MM3 ∗ and CVFF provide conformer distributions which account for the solution NMR observables in a satisfactory way. AMBER/Homans provide a reasonable agreement, while conformational analysis of oligosaccharides by AM1, ESFF, and CFF91 is not advised. The best fit between the experimental X-ray distances and angles and the modeling studies is found when CVFF is used. Results from the different force fields (and AM1) for C-lactose were compared.