CONFBIO · Conformations and Interactions of Biologically Relevant Molecules
FP7 — People (Marie Curie Actions)
- Duration
- 2013-05-01 → 2017-06-28
- EU contribution
- €100,000
- Participants
- 1
- Scheme
- MC-CIG
Lines connect the coordinator with its partners.
Results in brief
Conformations and Interactions of Biologically Relevant Molecules
Over the four year period of the Marie Curie CIG Fellowship, a new 2-8 GHz broadband rotational spectrometer unique in the UK has been designed and set up, and it is fully operational. The spectrometer implements bespoke heating and laser ablation nozzles, which allow the investigation of liquids with low vapour pressures and organic solids. With this instrument several archetypal odorants and their interactions with water and ethanol have been studied, obtaining new conformational and structural data, and benchmarking theoretical approaches. Results from these investigations made clear that an accurate description of dispersion interactions, which are significant as molecular size increases, is still a challenge for theoretical methods. The study of complexes with water revealed a remarkable number of configurations of water molecules around odorants, which yields information on the first steps of solvation. Studies with ethanol provide the first glimpse on the interaction of mimics of amino acid side chains with odorants. In addition, computational calculations on modified amino acids have been performed. The fellow holds a permanent position at her host institution and has established her own laboratory as an independent researcher. She has established new collaborations with researchers at the host institution and beyond, and with industry. The support of the host institution and the award of a Marie Curie CIG have been crucial for the development of the research activities of the fellow.
Data: CORDIS, © European Union
Project objective
Biological processes like molecular recognition, membrane transport, and folding and unfolding of proteins occur when the molecules involved have appropriate structures and interact in a specific way. However, a detailed knowledge of the structures of biologically-relevant molecules and the forces that give rise to them is still lacking for many processes. The aim of this project is to determine the structures of biologically relevant molecules and their interactions. We will examine the conformational space of several chiral odorants to explore the possible link between conformational flexibility and enantiomeric discrimination of odorants. We will study carvone, nootkatone and methyl-gamma-cyclogeranate, with enantiomers that smell differently, and fenchone, gamma-octathionolactone and tetrahydronootkatone, with enantiomers that smell the same. Interactions between these odorants and receptors in the ligand-binding site will be modeled by studying complexes formed between odorants and mimics of amino acid residues. The results will help gain insight into the molecular mechanisms of olfaction. We will also study changes induced by post-translational modifications, specifically glycosylation, phosphorylation and acetylation. Post-translational modifications of proteins that alter amino acid side chains exert a great influence in overall protein conformation, function, stability and dynamics. We will investigate the conformational landscape of several modified amino acids to determine their preferred structures and the relevant intramolecular forces that stabilise them. The results will yield new experimental data of immediate use for the bioinformatics community. To conduct this research a novel instrument combining broadband rotational spectroscopy with heating and laser ablation will be built. This instrument will be an invaluable resource for structural studies that will outlast the duration of this research project
Original text from CORDIS.
Participants
- KING'S COLLEGE LONDON · LondonCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union