Parameters for the calculation of proton NMR chemical shifts of oligoribonucleotides.

A set of empirical parameters which allows the prediction of the proton NMR chemical shifts at 70 C of non-exchangeable heterobase and anomeric protons in oligoribonucleotides has been constructed. The set is based on the highly flexible nature of oligoribonucleotide single strands and the wide range of conformational states which can be populated at relatively high temperatures (70 C or greater). A pairwise subtractive procedure, using 129 ribonucleotide oligomers (all 16 dimers, all 64 trimers, 37 tetramers, and 12 pentamers), shows that significant contributions to the observed chemical shift of protons in a given nucleoside residue are made by first, second, and third neighbors on the 3' and the 5' sides. The majority of the neighbors cause shielding effects with the exception of some first neighbors on the 5' side of a given residue. The magnitude of the shielding effects is greatest for the purine heterobases and follows the order A greater than G greater than C greater than U, with first neighbors on the 3'side showing more pronounced effects than second neighbors and these in turn showing larger effects than third neighbors. Second neighbors on the 5' side showed consistently greater shieldings than first neighbors, a result attributed to the deshielding effects of the first 5' neighbor phosphate group. The parameter Tables are applied to the prediction of proton chemical shifts in one heptamer, four hexamers, and two pentamers and give average absolute differences between predicted and observed shifts less than 0.030 ppm. The parameter approach represents an excellent method of generating initial assignments of proton chemical shifts for any single strand oligoribonucleotide.