Stereochemistry and Protein Folding: Spectroscopic and Molecular Dynamics Studies of Homopolypeptides in DMSO

Abstract

In addressing stereochemistry for likely relevance in protein folding, poly-L and alternating-L,D diastereomers of suitable homopolypeptides have been evaluated for effects of solvent with spectroscopy and statistical-mechanical modeling. Previous studies have shown that the models are contrasted in effect of water and methanol as the solvents.1-3 A lysine-solubilized nonapeptide now studied for conformation as a function of stereochemistry, has been found based on NMR, to be unfolded in DMSO irrespective of stereochemistry. Molecular-dynamics studies concur with the results, showing that indeed the diastereomers are populated in beta-basins of phi, psi space and are unfolded in conformation. The contrasts of water, methanol, and DMSO as the solvents for the diastereomeric structures of the model peptides are discussed in relation to the proposed protein-folding model according to which poly-L stereochemistry is the fulcrum placing hydrogen bonds and electrostatics of polypeptide dipoles in mutual conflict, and thus conformation under dielectric control. The solvent role in protein folding will be discussed for its physical basis.