Untitled

Abstract

The cross-peaks of 1H-NOESY spectra at different time delays are compared to a mode-coupling diffusion (MCD) calculation, including the evaluation of the full 1H relaxation matrix, in the case of a 23 nucleotide fragment of the stem-loop SL1 domain of HIV-1Lai genomic RNA mutated in a single position. The MCD theory gives significant agreement with 1H 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.

Molecular dynamics of C-peptide of ribonuclease A studied by replica-exchange Monte Carlo method and diffusion theory

“…In this subsection we briefly review recent advances of diffusion theory [6,7] that are applied to the calculation of the 1 H-NOESY NMR cross peak intensities (CPs). The CP intensities O h,k at mixing time t m between spin h and spin k can be calculated by the following equation:…”

“…[6,7] for details). In the present work, we use the replica-exchange Monte Carlo method for the calculation of these averages (see Eq.…”

“…This equation has been solved by matrix expansion methods and by using a mode-coupling approximation [6,7]. This procedure allows the description of the time-correlation functions (TCFs) that govern NMR experiments through the computation of a suitable set of configurational averages.…”

Modeling the dynamics of the solvated SL1 domain of HIV‐1 genomic RNA

“…This domain has the form of a hairpin that is organized in a stem‐loop structure with the sequence CUUGCUGAAGCGCGCACGGCAAG. In order to study the dynamic properties of the SL1 stem‐loop in its monomeric form, the nucleotide G12 has been mutated into A12, to prevent the spontaneous dimerization process of the oligonucleotide in the NMR experiments 36, 38. The detailed description of NMR experiments and of MD simulation can be found in the references above.…”

“…In a recent article the dynamics of a mutated stem‐loop SL1 domain of HIV genomic RNA have been studied by MCD‐MD and the results have been compared to experimental data obtained by 1 H nuclear Overhauser effect spectroscopy (NOESY) NMR spectroscopy 36. Among the experimental data, the H5—H6 intraresidue cross peaks (CPs) of U and C bases were found sensitive both to the global rotational dynamics and to the different mobility of the loop compared to the stem.…”