Research in the

Gerig Group


Department of Chemistry and Biochemistry


Write-ups & Software


Getting to UCSB

Useful Links

Small Molecule-Peptide Interactions

Laboratory studies of peptides and proteins may give an incomplete picture of the structures of these molecules and how they achieve their biological effects. Such studies typically examine materials that are highly homogeneous, dissolved in well-defined solutions that may contain a simple buffer system and perhaps some salt. The cellular environment where the subject molecule actually operates may be much more complex, containing high concentrations of many large and small molecules.
       Developments in our group over the past few years have provided NMR tools for study of the interactions of small molecules with peptide or proteins. A particular focus has been intermolecular nuclear Overhauser effects (NOEs) that arise through magnetic interactions between spins associated with the solvent and those of a solute.

Interpretation of results of the intermolecular NOE experiments usually is done using a model of the system of interest that treats all molecules as non-interacting hard spheres. This approach often predicts outcomes that agree with experimental results. Unusual solvent-solute interactions are indicated when such agreement is absent. A hard spheres model is not necessarily appropriate for use with molecules as complicated as a protein and it is difficult to generate understanding of any solvent-solute system at the molecular level when the hard spheres model fails. For these reasons, we are developing molecular dynamics (MD) simulations of the systems of interest to aid in interpretation of experimental observations 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).