Sulfur-Aromatic INteraction in BIOmolecules: Structural Investigations and Spectroscopy – SAINBIOSIS

Recent bioinformatics studies on protein structure databases have revealed that one third of all known proteins have their structure stabilized by non-covalent interactions between sulfur and pi electrons of aromatic groups, called S-pi interactions. Due to the change in the electron orbitals, S-pi interacting groups are also involved as relay stations in the electron transport processes within proteins. The biological relevance of this interaction is also imparted by its implication in pathologies associated with the interaction loss due to sulfur oxidation, including aging-related diseases such as Alzheimer or Creutzfeldt-Jacob. S-pi interactions are gaining interest in many research areas, for the development of new drugs for targeted therapeutics, the design of organo-catalysts and for the understanding of the structure and functions of biological systems. However, there is, to date, no spectroscopic fingerprint of this interaction which, in addition to bringing information on the electronic structure, charge transfers and derived properties of sulfur and aromatic containing-proteins, could provide a Biomarker of the protein denaturation for the early detection of some pathologies. With this project, our teams aim at employing advanced gas-phase spectroscopic tools (IR, UV/VUV and X-ray spectroscopy) in combination with mass spectrometric techniques to unravel the fingerprints of the S-pi interactions in peptides and proteins. Fundamental effects of the sulfur oxidation on the protein's denaturation and changes in the spectroscopic signature will also be studied. This experimental work is supported by theoretical calculations where the s-pi interaction and the rest of the molecule are treated by ab initio methods (QM) and molecular mechanics (MM), respectively. The spectra calculation might require as well clustering techniques to provide an estimate of the important conformers to identify key features in stabilizing protein structure via S-pi interactions.