NMR Studies on the Structure and Functions of Small Biomolecules with Highly Flexible Conformation

Abstract In this review, we deal with the flexible structures of small biomolecules and discuss how spontaneous conformational changes are related to their biological functions, mainly focusing on our recent research results. In particular, we applied nuclear magnetic resonance (NMR)-based methods to biomolecules that largely comprise methylene-dominant chain(s) by observing spin-spin coupling constants in solution NMR and quadrupolar interactions and chemical shift anisotropy in solid-state NMR. In the study of spermidine and spermine, we investigated how the shape of a molecule changes when the ammonium groups interact with polyanions such as ATP. In membrane lipid studies, we examined the orientation and conformation of the choline phosphate moiety in the hydrophilic head group of membrane lipid molecules, and the average structure and fluctuations of the fatty acids, which were mainly alkane chains in the hydrophobic part. In these structural studies, the goal was not to determine the predominant conformation of biomolecules, but to elucidate the average conformation of multiple conformers that were interchanging at high speed. We used physicochemical parameters to describe the changes in the average structure of lipid in membranes. Computational methods were adopted to estimate the structural changes in molecules, but experimental results are still important to judge the reliability of the calculation results. Through these studies, we discuss how the flexibility of biomolecules is involved in the expression of biological function.