FORMATION OF NOVEL BASE TRIPLET STRUCTURES BY ISOMORPHIC REPLACEMENT

通过同构置换形成新型碱基三重态结构

• 批准号: 6220351
• 负责人: BERNHARD J WALBERER
• 金额: $ 0.01万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6220351
• 关键词: AIDS; biomedical resource; computers; enzymes; immunology; infection; inflammation; lymphatic system; virus

A complete database of base pairs and base triplets was constructed by computer modeling based solely on geometric principles. This database comprises all experimentally known base pairs and base triplets and a much larger number of base pairs and base triplets that have so far not been observed in nature. Various computer programs have been developed that identify base combinations with high intrinsic stabilities and that classify base combinations according to certain structural criteria such as the ability to overlap in the positions of the glycosidic bonds. We are now in the process of systematically testing the hypothesis that it is possible to form novel base triplets by using structurally similar base triplets in known nucleic acid structures as scaffold. In order to prove the feasibility of this strategy it is necessary to model each novel base triplet in the context of the overall RNA structure, e.g. to check for potential steric conflicts and for the disruption of other stabilizing interactions upon substitution of the known base triplet. This task can best be accomplished by interactive molecular modeling on computers with advanced graphics capabilities. These modeling studies are initially limited to already known three-dimensional RNA structures such as tRNAs although it is planned to extend these studies to the design of novel types of RNA structure.

一个完整的碱基对和碱基三联体数据库， 完全基于几何学原理的计算机建模所构建的。 该数据库包括所有实验已知的碱基对和碱基 三联体和大量的碱基对和碱基三联体， 到目前为止还没有在自然界中观察到。 各种计算机程序 已经开发了识别具有高 内在稳定性和根据 某些结构标准，例如在 糖苷键的位置。 我们现在正在 系统地验证了一个假设，即有可能形成 通过使用结构相似的碱基三联体， 已知的核酸结构作为支架。 为了证明 为了验证这一策略的可行性，有必要对每个新基地进行建模 在整个RNA结构的背景下，检测三联体，例如， 潜在的空间冲突和其他稳定的破坏 已知碱基三联体取代后的相互作用。 此任务 最好通过交互式分子建模来实现， 具有高级图形功能的计算机。 这些模型研究 最初仅限于已知的三维RNA 尽管计划将这些结构扩展到 设计新型RNA结构的研究。