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

该奖项将支持斯蒂芬博士与 位于伯明翰的亚拉巴马大学的哈维和理查德博士 Lavery，Institut de Biologie Physico-Chimique，巴黎，法国。 的 该项目的目标是研究核酸双螺旋 根据其主要的碱基序列。 JUMNA（核酸的连接建模），由 Lavery博士和他的合作者，是用来模拟各种 DNA结构。 该计划也将被修改，以转换它 从结构优化算法到分子动力学 算法 关于DNA结构，有两类问题 将被调查。 第一，DNA序列之间的关系 双螺旋结构的局部变化 研究的目的是了解（1）DNA的起源 弯曲和（2）蛋白质如何识别DNA序列， 结构上的细微变化。 第二，将建立模型， 与聚嘌呤-聚嘧啶序列相关的结构， 复制和转录。 在模型结构中 元件将是茎环结构，单链，螺旋 有两条、三条和四条链， 这些不同的元素。 这些研究不仅意义重大， 因为它们提供了对DNA结构的深入了解， 开发的方法将有助于检查其他建模 DNA和RNA的问题。 凭借从以下方面获得的经验 在这些研究中，研究人员将转向以下问题： 将JUMNA转换为分子动力学算法 模拟核酸。 后一个项目如果成功， 将允许在更大的系统上进行模拟， 在更长的时间尺度上， 分子动力学算法 由双方领导的研究小组 哈维博士和莱弗里博士在这方面做出了重要贡献。 核酸模拟领域。 模拟的进展 方法对于NAs比对于蛋白质慢得多。 工作 这两个群体所做的工作是独特的，也是重要的贡献。 预计拟议的合作将加快以下方面的进展： 该领域

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.