Modeling the dynamics of a mutated stem-loop in the SL1 domain of HIV-1 (Lai) genomic RNA by 1H-NOESY spectra

The cross-peaks of H-1-NOESY spectra at different time delays are compared to a mode-coupling diffusion (MCD) calculation, including the evaluation of the full H-1 relaxation matrix, in the case of a 23 nucleotide fragment of the stem-loop SL1 domain of HIV-1(Lai) genomic RNA mutated in a single position. The MCD theory gives significant agreement with H-1 relaxation experiments enabling a thorough understanding of the differential local dynamics along the sequence and particularly of the dynamics of nucleotides in the stem and in the loop. The differential dynamics of this hairpin structure is important in directing the dimerization of the retroviral genome, a fundamental step in the infectious process. The demonstration of a reliable use of time dependent NOE cross-peaks, largely available from NMR solution structure determination, coupled to MCD analysis, to probe the local dynamics of biological macromolecules, is a result of general interest of this paper.