Effects caused by fluorine on physical chemistry properties of amino acids and proteins

Abstract

A theoretical and experimental study is proposed, which comprises theoretical calculations of high-level electronic structure and studies by infrared and NMR spectroscopies of 1H, 13C and 19F amino acids and fluorinated proteins, which may present intramolecular hydrogen bonds, hyperconjugative interactions and steric effects that may directly affect the biological properties of these molecules. At first, it is intended to carry out theoretical conformational studies of these molecules in solution, using high-level ab initio and functional DFT methods with different sets of bases, to identify the population of the confomers and their energetic contributions to the main structure. Then, the experimental spectroscopic studies of the compounds will be carried out to validate the theoretical results. Finally, it is intended to perform simulations for the protein-ligand and enzyme-substrate systems, by means of molecular dynamics and QM/MM calculations (Quantum Mechanics / Molecular Mechanics), of fluorinated proteins containing the amino acids 4-fluorothreonine, 4R(S)-fluoro-proline and 5-fluoro-tryptophan.