MOLECULAR DYNAMICS STUDIES OF RIBONUCLEIC ACID STRUCTURE AND FUNCTION: HIV MRNA

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ribonucleic acid (RNA) recognition is essential to many cellular and viral processes, including 5-capping, polyadenylation, RNA splicing and translation. RNA is particularly complex because the target molecules can adopt a wide variety of secondary and tertiary structures. Molecular dynamics (MD) simulations can provide a detailed three-dimensional representation of RNA throughout time. Three molecular dynamics studies are proposed to elucidate mechanisms of RNA recognition by modeling RNA molecules, discerning how changes to the sequence, chemical structure and ion presence affect RNA structure and function. All simulations are run in explicit solvent (TIP3P) with the Cornell et al. (J. Am. Chem. Soc., 1994, 117, 5179) forcefield, particle mesh Ewald formalism to account for electrostatics using the program AMBER (Case, D.A. et al. 2004). Three systems are studied at the atomistic level using MD simulations. The first study examines the role of nonstandard nucleic acid bases in altering transfer RNA (tRNA) structure. The second study computationally models sequence variation in small interfering RNAs in an effort to rationalize otherwise inexplicable experimental data. The third examines differences in recognition of human immunodeficiency messenger RNA by a viral peptide and a synthetic peptide, RSG 1.2. All MD studies will seek to systematically characterize protein-RNA interactions or RNA structure on a chemical level to provide a better understanding of the relationship between RNA structure and function.