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Molecular dynamics simulations and 2D-NOESY spectroscopy were applied to study the conformations and hydrogen-bonding interactions of ACE-inhibitory tripeptide Gly-Glu-Phe (GEF) in aqueous and DMSO solutions. The properties of GEF in simulations were characterized by intramolecular distance, root-mean-square deviation, solvent-accessible surface, and radius of gyration. Interestingly, the GEF molecule showed different behavior in different solvents. In aqueous solution, the GEF was highly flexible, and it could quickly convert from extended state to folded state. However, in DMSO solution, the extended conformations were hardly observed. The GEF molecule preferred extended state in aqueous compared to DMSO solution, which was confirmed by 2D-NOESY. [ABSTRACT FROM AUTHOR]

Abstract: Riboswitches are RNA-based genetic control elements that function via a conformational transition mechanism when a specific target molecule binds to its binding pocket. To facilitate an atomic detail interpretation of experimental investigations on the role of the adenine ligand on the conformational properties and kinetics of folding of the add adenine riboswitch, we performed molecular dynamics simulations in both the presence and the absence of the ligand. In the absence of ligand, structural deviations were observed in the J23 junction and the P1 stem. Destabilization of the P1 stem in the absence of ligand involves the loss of direct stabilizing interactions with the ligand, with additional contributions from the J23 junction region. The J23 junction of the riboswitch is found to be more flexible, and the tertiary contacts among the junction regions are altered in the absence of the adenine ligand; results suggest that the adenine ligand associates and dissociates from the riboswitch in the vicinity of J23. Good agreement was obtained with the experimental data with the results indicating dynamic behavior of the adenine ligand on the nanosecond time scale to be associated with the dynamic behavior of hydrogen bonding with the riboswitch. Results also predict that direct interactions of the adenine ligand with U74 of the riboswitch are not essential for stable binding although it is crucial for its recognition. The possibility of methodological artifacts and force-field inaccuracies impacting the present observations was checked by additional molecular dynamics simulations in the presence of 2,6-diaminopurine and in the crystal environment. [Copyright &y& Elsevier]