Molecular Dynamics of Induced Fit in U1A-RNA Complexes

U1A-RNA 复合物中诱导拟合的分子动力学

• 批准号: 7089905
• 负责人: BETHANY L KORMOS
• 金额: $ 4.88万
• 依托单位: WESLEYAN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-05 至 2007-07-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7089905
• 关键词: RNA; RNA binding protein; binding sites; chemical structure function; computer simulation; intermolecular interaction; molecular assembly /self assembly; molecular dynamics; postdoctoral investigator; small nuclear ribonucleoproteins; thermodynamics

DESCRIPTION (provided by applicant): The objective of this research is to investigate induced fit phenomena involved in the formation of protein- RNA complexes using molecular dynamics (MD). Protein-RNA complexes are involved in all steps of mRNA processing and, as such, a complete understanding of the post-transcriptional regulation of gene expression is dependent upon knowledge of how protein-RNA recognition occurs. This investigation will be accomplished using several theoretical techniques. A study of the induced fit processes in protein-RNA complexes will be performed by investigating changes in structure and motions of complexes, uncomplexed forms, amino acid mutants and RNA base pair modifications of the U1A-stem loop 2 RNA system using all atom MD simulations. Contributions of the induced fit process to configurational entropy, binding affinity and specificity involved in U1A-RNA complexation will then be determined using free energy simulations and MMPBSA component analysis. Finally, using U1A-RNA as a prototype case, other theoretical means for studying protein-RNA complexes will be investigated, including MD in a PBSA solvent, hybrid QM/MM techniques, and variations on MD methodologies extended to larger time steps or reduced representations.

描述（由申请人提供）： 本研究的目的是利用分子动力学 (MD) 研究蛋白质-RNA 复合物形成中涉及的诱导拟合现象。蛋白质-RNA 复合物参与 mRNA 加工的所有步骤，因此，对基因表达转录后调控的完整理解取决于对蛋白质-RNA 识别如何发生的了解。这项研究将使用多种理论技术来完成。将通过使用全原子 MD 模拟研究 U1A-茎环 2 RNA 系统的复合物结构和运动、未复合形式、氨基酸突变体和 RNA 碱基对修饰的变化来研究蛋白质-RNA 复合物中的诱导拟合过程。然后将使用自由能模拟和 MMPBSA 成分分析来确定诱导拟合过程对 U1A-RNA 络合中涉及的构型熵、结合亲和力和特异性的贡献。最后，使用 U1A-RNA 作为原型案例，将研究研究蛋白质-RNA 复合物的其他理论方法，包括 PBSA 溶剂中的 MD、混合 QM/MM 技术以及扩展到更大时间步长或减少表示的 MD 方法的变体。