US-France Cooperative Research: Conformation and Dynamics of Nucleic Acids

美法合作研究：核酸的构象和动力学

• 批准号: 8815910
• 负责人: Stephen Harvey
• 金额: $ 1.06万
• 依托单位: University of Alabama at Birmingham
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-03-01 至 1992-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8815910&HistoricalAwards=false
• 关键词: US; France; Cooperative; Research; Conformation

This award will support collaborative research between Dr. Stephen Harvey, University of Alabama at Birmingham, and Dr. Richard Lavery, Institut de Biologie Physico-Chimique, Paris, France. The objective of the project is to study the nucleic acid double helix structure in terms of its primary base sequence. JUMNA (Junction Modeling of Nucleic Acids), a program developed by Dr. Lavery and his collaborators, is to be used to model various DNA structures. The program will also be modified to convert it from a structure optimization algorithm to a molecular dynamics algorithm. With regard to DNA structure, two classes of problems will be investigated. First, the relationship between DNA sequence and the variations in the local structure of the double helix will be examined, with the goal of understanding (1) the origins of DNA bending and (2) how proteins might recognize DNA sequences through subtle changes in structure. Second, models will be built for structures associated with polypurine-polypyrimidine sequences and with replication and transcription. Among the model structural elements will be stem-loop structures, single strands, helices containing two, three, and four strands, and the junctions between these various elements. These studies will be significant not only for the insights they provide into DNA structure, but because the methods developed will be useful for examining other modeling problems for both DNAs and RNAs. With the experience gained from these studies, the investigators will then turn to the problem of converting JUMNA into an algorithm for molecular dynamics simulations on nucleic acids. This latter project, if successful, would allow simulations to be performed on much larger systems and over much longer time scales than is possible with current molecular dynamics algorithms. The research groups headed by both Dr. Harvey and Dr. Lavery have made important contributions in the area of simulation of nucleic acids. Progress in simulation methods has been much slower for NAs than for proteins. The work done by these two groups is unique and an important contribution. The proposed collaboration is expected to accelerate progress in this field.

该奖项将支持阿拉巴马大学伯明翰分校的 Stephen Harvey 博士和法国巴黎生物物理化学研究所的 Richard Lavery 博士之间的合作研究。 该项目的目标是研究核酸双螺旋结构的一级碱基序列。 JUMNA（核酸连接建模）是 Lavery 博士及其合作者开发的一个程序，用于模拟各种 DNA 结构。 该程序还将被修改，将其从结构优化算法转换为分子动力学算法。 关于DNA结构，将研究两类问题。 首先，将检查 DNA 序列与双螺旋局部结构变化之间的关系，目的是了解 (1) DNA 弯曲的起源以及 (2) 蛋白质如何通过结构的细微变化来识别 DNA 序列。 其次，将为与多嘌呤-多嘧啶序列以及复制和转录相关的结构建立模型。 模型结构元件包括茎环结构、单链、包含两条、三条和四条链的螺旋，以及这些不同元件之间的连接。 这些研究不仅因为它们提供了对 DNA 结构的见解而具有重要意义，而且因为所开发的方法将有助于检查 DNA 和 RNA 的其他建模问题。 凭借从这些研究中获得的经验，研究人员将转向将 JUMNA 转换为核酸分子动力学模拟算法的问题。 后一个项目如果成功，将允许在比当前分子动力学算法更大的系统和更长的时间尺度上进行模拟。 Harvey博士和Lavery博士领导的研究小组在核酸模拟领域做出了重要贡献。 NA 的模拟方法的进展比蛋白质的模拟方法要慢得多。 这两个小组所做的工作是独特且重要的贡献。 拟议的合作预计将加速该领域的进展。