Ab initio calculations of NMR chemical shifts for structure determination in biology

Abstract

In this thesis we present an application of a computational method for calculating nuclear Magnetic Resonance chemical shifts to structure determination in Biology. We investigate and summarise the most important structural contributions to the chemical shift. Even though the NMR chemical shift has direct relation to the global structure it is shown that there are two main dominant contributions: I3C-a depends mainly on the secondary structure and 15-N NMR chemical shift depends mainly on hydrogen bonds. The importance of other relevant contributions to the chemical shifts, such as solvent and dynamical effects, is demonstrated by testing our computational method on proteins and by comparing theory and experiment. The thermal effects on the chemical shift in the solid are studied by combinig ab initio molecular dynamics simulations and NMR chemical shift calculations. Other factors affecting the chemical shift are investigated by constructing ideal models from which we can extract information about the nature of the hydrogen bonds in helical structures. By doing these calculations we suggest specific experimental measurements of chemical shift which could differentiate structures that have minor structural variations between them, eg. the three different types of helices in proteins. The last topic studied in this thesis, namely amyloid fibrils, is presented as a starting point for future work.