Dynamic Descriptions of Highly Flexible Molecules from NMR Dipolar Couplings: Physical Basis and Limitations

J Am Chem Soc. 2017 Apr 12;139(14):5011-5014. doi: 10.1021/jacs.7b01566. Epub 2017 Mar 29.

Abstract

Biomolecules that control physiological function by changing their conformation play key roles in biology and remain poorly characterized. NMR dipolar couplings (DCs) depend intrinsically on both molecular shape and structural fluctuations, thereby providing the enticing prospect of tracking these conformational changes at atomic detail. Although this dual dependence has until now severely complicated analysis of DCs from highly dynamic systems, general approaches have recently been proposed that simplify interpretation of experimental DCs, by entirely eliminating molecular alignment from the analysis. Using simple and intuitive simulation of target ensembles, we investigate the impact of such approaches on the resulting descriptions of the conformational energy landscape. We find that ensemble descriptions of highly flexible systems derived from DCs without explicit consideration of the alignment properties of the constituent conformations can be compromised and inaccurate, despite exhibiting high correlation with experimental measurement.