Bringing Machine‐Learning Enhanced Quantum Chemistry and Microwave Spectroscopy to Conformational Landscape Exploration: the Paradigmatic Case of 4‐Fluoro‐Threonine
Vincenzo Barone, Marco Fusè, Raúl Aguado, Simone Potenti, Íker León, Elena R. Alonso, Santiago Mata, Federico Lazzari, Giordano Mancini, Lorenzo Spada, Andrea Gualandi, Pier Giorgio Cozzi, Cristina Puzzarini, José L. Alonso
Abstract
A combined experimental and theoretical study has been carried out on 4-fluoro-threonine, the only naturally occurring fluorinated amino acid. Fluorination of the methyl group significantly increases the conformational complexity with respect to the parent amino acid threonine. The conformational landscape has been characterized in great detail, with special attention given to the inter-conversion pathways between different conformers. This led to the identification of 13 stable low-energy minima. The equilibrium population of so many conformers produces a very complicated and congested rotational spectrum that could be assigned through a strategy that combines several levels of quantum chemical calculations with the principles of machine learning. Twelve conformers out of 13 could be experimentally characterized. The results obtained from the analysis of the intra-molecular interactions can be exploited to accurately model fluorine-substitution effects in biomolecules.