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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 核糖核酸（RNA）识别对于许多细胞和病毒过程是必不可少的，包括5-加帽、聚腺苷酸化、RNA剪接和翻译。RNA是特别复杂的，因为靶分子可以采用各种各样的二级和三级结构。分子动力学（MD）模拟可以提供RNA在整个时间内的详细三维表示。提出了三个分子动力学研究来阐明RNA识别的机制，通过建模RNA分子，识别序列，化学结构和离子存在的变化如何影响RNA的结构和功能。所有模拟均在显式溶剂（TIP 3 P）中进行，Cornell等人（J. Am.化学会，1994，117，5179）力场，粒子网格Ewald形式主义使用AMBER程序来解释静电（Case，D.A.等人，2004）。三个系统进行了研究，在原子水平上使用MD模拟。第一项研究检查了非标准核酸碱基在改变转移RNA（tRNA）结构中的作用。第二项研究通过计算模拟了小干扰RNA的序列变异，试图使其他无法解释的实验数据合理化。第三个检查识别人类免疫缺陷信使RNA的病毒肽和合成肽，RSG 1.2的差异。所有MD研究将寻求在化学水平上系统地表征蛋白质-RNA相互作用或RNA结构，以更好地理解RNA结构和功能之间的关系。

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.