Efficient exploration of conformational space using the stochastic search method: application to β-peptide oligomers

Abstract

An efficient and general strategy for the determination of all low-energy minima of a molecule, viz., the stochastic conformational jump procedure, has been implemented in the BOSS package. In this method, a new structure is generated by random movement ("kick") of individual atoms with a predefined maximum displacement, and the resultant geometry is optimized. Using the OPLS-AA force field, two series of oligomers of β-amino acids with methyl ester terminal groups have been chosen for detailed examination. Monomeric (S)-3-pyrrolidine-3-carboxylic acid (PCA) and (S)-nipecotic acid (Nip) have 4 and 2 nearly equi-energy conformers, respectively. The dimers and trimers have substantially larger number of low-energy conformers within 1 kcal/mol of the global minimum. However, the low-energy conformers of the tetramers can all be classified as belonging to a few distinct families, in terms of variations in total interatomic distances. Even in the absence of hydrogen bonding, the larger oligomers have two well-defined conformers, a compact helical form, and an extended structure. The preferences for these forms are determined exclusively by intramolecular dipolar interactions and van der Waals' forces. These results are consistent with experimental CD spectral trends, which reveal sharp features only for the higher oligomers (n>3).