Validation of two conformational searching methods applied to sucrose: simulation of NMR and chiro-optical data

Abstract

The potential energy hypersurface of sucrose has been examined by molecular mechanics calculations (MM3(92)) interfaced with two different algorithms for conformational searching. The first uses the systematic grid-search approach. The second algorithm, which has a lower CPU requirement, is the so-called CICADA procedure (Channels In Conformational space Analyzed by Driver Approach). This method drives selected torsional angles to explore the low-energy regions and permits full geometry relaxation. Using the grid-search approach, the adiabatic relaxed map of sucrose was calculated as a function of the glycosidic torsion angles, and three families of stable conformers were identified. The CICADA procedure found all minima and also the low-energy conversion pathways for the disaccharide in agreement with those located by the grid-search approach. The method appears to be more efficient for determining the global energy minimum. Beside locating structures at energy minima, transition states and low-energy pathways were also identified. In order to assess the validity of the potential energy surfaces, comparisons were made between experimental and theoretical values of some spectral properties. Optical rotation values were taken from the literature, whereas the NOESY volumes were measured at 400 MHz. Theoretical data were calculated taking into account all the accessible conformations derived from either the grid-search or the CICADA method. NMR relaxation data were calculated using averaging methods appropriate for both slow and fast internal motions. The present study demonstrates the ability of the new CICADA method to reproduce the potential energy surface of a flexible molecule and therefore successfully to simulate its spectral properties.