DFT Calculation of Nitrogen Chemical Shifts in the Active Site of Vitamin D Receptor

The complexed vitamin D receptor (VDR) is responsible for calcium homeostasis. Tryptophan is of special importance for the receptor's functions, as it appears just once in the VDR sequence and occupies the center of the ligand binding pocket. DFT calculations of nitrogen chemical shifts for Trp-NHSC moiety, presented in thiswork for liganded and free receptor, agree with NMR studies on the VDR specifically labeled with [UL] 15N2 Trp. Our calculations confirm orientation of the C(7)=C(8) vitaminDbond under the tryptophan ring. We suggest that interactions with water molecules are responsible for observed deshielding of indole Trp-nitrogen in unliganded VDR.