VALIDATION OF 2 CONFORMATIONAL SEARCHING METHODS APPLIED TO SUCROSE -SIMULATION OF NMR AND CHIRO-OPTICAL DATA

The potential energy hypersurface of sucrose has been examined by mole cular mechanics calculations (MM3(92)) interfaced with two different a lgorithms for conformational searching. The first uses the systematic grid-search approach. The second algorithm, which has a lower CPU requ irement, is the so-called CICADA procedure (Channels In Conformational space Analyzed by Driver Approach). This method drives selected torsi onal angles to explore the low-energy regions and permits full geometr y relaxation. Using the grid-search approach, the adiabatic relaxed ma p of sucrose was calculated as a function of the glycosidic torsion an gles, and three families of stable conformers were identified, The CIC ADA procedure found all minima and also the low-energy conversion path ways for the disaccharide in agreement with those located by the grid- search approach. The method appears to be more efficient for determini ng the global energy minimum, Beside locating structures at energy min ima, transition states and low-energy pathways were also identified. I n order to assess the validity of the potential energy surfaces, compa risons were made between experimental and theoretical values of some s pectral properties, Optical rotation values were taken from the litera ture, whereas the NOESY volumes were measured at 400 MHz, Theoretical data were calculated taking into account all the accessible conformati ons derived from either the grid-search or the CICADA method. NMR rela xation data were calculated using averaging methods appropriate for bo th slow and fast internal motions, The present study demonstrates the ability of the new CICADA method to reproduce the potential energy sur face of a flexible molecule and therefore successfully to simulate its spectral properties. (C) 1997 Elsevier Science B.V.