Understanding the effect of solvation on the structure of ion-peptide complexes, one water molecule at a time
Final Report Abstract
It is well known that the electric fields of metal ions affect the structure and function of biomolecules. A particularly prominent example are enzymes, as their catalytic function is highly dependent on local electric fields surrounding the active site. Because of the complexity of condensed phase systems, however, a molecular level understanding of the function of those biomolecular systems is often lacking. A way to obtain such insights is to simplify the systems, study these smaller model systems in detail, and then increase the complexity sequentially to be able to make meaningful comparisons to biologically relevant systems. The solvation of alkali metal ionpeptide complexes is a good example of such a simple model system, as the complexity can be easily enhanced by increasing the number of solvent molecules as well as the peptide chain length. By variation of the metal ion in these complexes, their impact on the structure of these can be studied on a molecular level, which is done throughout this project using cryogenic infrared action spectroscopy in the gas phase. Even in a peptide as small as diglycine, the electric field of the metal ion impacts the structure of the complex. The smaller the ion, the larger the electric field that the peptide experiences due to the smaller metal ion-peptide distance. The electric field of the metal ion polarises the bonds in the peptide yielding a change in strength of an internal hydrogen bond in the peptide backbone, which was found to be strongest for Li+ and weakest for K+ due to these electric field differences. This is particularly interesting because the metal ion is binding to the peptide from the other end of the molecule, meaning that the modulation of the strength of this hydrogen bond is done remotely, showcasing the long-range impact of this electrostatic metal ion-peptide interaction. By adding solvent to these complexes, the strength of this internal hydrogen bond in the peptide backbone is weakened, even though the water binds to the metal ion without additional peptide interactions. This is because the water is pulling the metal ion further away from the peptide, thereby weakening the electric field that the peptide experiences. This is different for the one water complex of K+, as the larger size of the metal ion and therefore, larger distance to the peptide, allows for an additional solvent-peptide interaction. This finding is particularly insightful as it shows that the weaker electrostatic interaction between the K+ ion and the peptide enables a larger structural flexibility, which is related to the permeability of K+ in potassium ion channels. By adding more solvent, the competition between solvent-peptide and solvent-metal ion interaction is further increased, as several different binding sites are possible. Due to a steeper decrease of the electric field strength upon solvation, it takes only two water molecules to change the preferred peptide conformation in case of Li+, whereas it takes three water molecules for the larger two metal ions. The addition of solvent does not only decrease the strength of the internal hydrogen bond in the peptide backbone, but also the strength of intermolecular hydrogen bonds between water and the peptide, which overall reduces the structural impact of the different metal ions on the peptides with increasing degree of solvation. This initiates the onset of the wealth of conformational flexibility in larger water clusters.
Publications
-
AN INTERNAL AFFAIR: THE INFLUENCE OF INTRAMOLECULAR HYDROGEN BONDING ON THE STRUCTURE OF METAL-ION-PEPTIDE COMPLEXES. Proceedings of the 2022 International Symposium on Molecular Spectroscopy, 1-1. University of Illinois at Urbana-Champaign.
Meyer, Katharina; Garand, Etienne & Nickson, Kathleen
-
The impact of the electric field of metal ions on the vibrations and internal hydrogen bond strength in alkali metal ion di-and triglycine complexes. The Journal of Chemical Physics, 157(17).
Meyer, Katharina A. E.; Nickson, Kathleen A. & Garand, Etienne
-
“A Little Friendly Competition: The Influence of Intramolecular Hydrogen Bonding on the Structure of Metal-Ion-Peptide Complexes and the Impact of Solvation”, Bunsen-Tagung, September 2022, Gießen, Germany.
K. A. E. Meyer & E. Garand
-
AN ELECTRIC AFFAIR: THE IMPACT OF SOLVATION ON THE STRUCTURE OF METAL ION-PEPTIDE COMPLEXES. Proceedings of the 2023 International Symposium on Molecular Spectroscopy, 1-1. University of Illinois at Urbana-Champaign.
Meyer, Katharina & Garand, Etienne
-
“An electric affair: The impact of solvation on the structure of metal ion-peptide complexes”, Bunsen-Tagung, June 2023, Berlin, Germany.
K. A. E. Meyer & E. Garand
-
„Oh so electric: How water solvation influences the structure and electric field strength in metal ion-peptide complexes”, GRC on Gaseous Ions, February 2023, Ventura, California, USA.
K. A. E. Meyer & E. Garand
