Addition of small molecules, such as an alcohol or an osmolyte, to aqueous solutions of peptides and proteins often alters the dominant conformation of these biomaterials. Why these effects occur is not always apparent, although at least in some cases it appears that selective interaction of the biomolecule with the small molecules is involved. Over the past few years, we have used heteronuclear and homonuclear intermolecular NOE experiments to examine such solvent-biopolymer interactions.

Interpretation of these NOE experiments can be done using a model of the system of interest that treats all molecules as hard spheres. This approach can produce predictions that agree with experimental results; unusual solvent-solute interactions are indicated when such agreement is absent. It is challenging to develop understanding of any solvent-solute system at the molecular level when the hard spheres model fails. We are, thus, developing all-atom molecular dynamics (MD) simulations of the systems of interest to aid in interpretation of experimental results previously reported from our lab.

Current efforts are focused on an analog of the peptide hormone angiotensin II, the mini-protein Trp-cage and melittin, a component of bee venom. Conformation-altering small molecules under study include various hydrocarbon and fluorocarbon alcohols and the osmolyte trimethylamine N-oxide (TMAO).