Modelling of molecular and chiral recognition by cyclodextrins. Is it reliable? Part 2. Molecular dynamics calculations in vacuum pertaining to the selective complexation of decalins by beta-cyclodextrin

Molecular modelling is frequently used to rationalize experimental findings concerning molecular and chiral recognition by cyclodextrins, although the reliability of neither molecular mechanics nor molecular dynamics in this domain has been extensively analyzed. We have recently started a program ai ming at the evaluation of computational methods applied in cyclodextrin res earch. After studying the complexes of decalin isomers with beta-cyclodextr in using molecular mechanics in the previous paper, in this work molecular and chiral recognition in the same systems was analyzed by molecular dynami cs in vacuum, using three different force fields and five values of dielect ric constant. The calculations using the AMBER FF resulted in the complexes decomposition. Those using CFF91 gave conflicting results, while CVFF calc ulations pertaining to molecular recognition for the complexes yielded cons istent results in qualitative agreement with experimental data. The simulat ions using CVFF and CFF91 for chiral recognition yielded equivocal results that lie within the limits of error. Therefore, contrary to established opi nion, we believe that molecular dynamics simulations in vacuum cannot yield reliable results pertaining to chiral recognition, in which very small ene rgy differences are involved. We also believe that, as concerns the studies of molecular recognition by cyclodextrins associated with considerably lar ger energy differences, such calculations, when carried out cautiously, may provide qualitative results.