Database for Modified Nucleotides, Fluorophors and Additives

修饰核苷酸、荧光团和添加剂数据库

• 批准号: 7049800
• 负责人: SVETLANA V MOROSYUK
• 金额: $ 12万
• 依托单位: DNA SOFTWARE, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-15 至 2006-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7049800
• 关键词: DNA primers; bioassay; biotechnology; chemical kinetics; computer program /software; computer simulation; computer system design /evaluation; conformation; fluorescent dye /probe; information systems; ionophores; nucleic acids; nucleotides; thermodynamics

DESCRIPTION (provided by applicant): The mission of DNA Software Inc. is to enable the field of genomics by writing enterprise grade simulation software that incorporates state-of-the-art knowledge of the thermodynamics and kinetics of nucleic acid folding and hybridization. To accomplish this goal, DNA Software has built the Oligonucleotide Modeling Platform (OMP), which accurately predicts target secondary structure, calculates probe hybridization thermodynamics, simulates DNA or RNA based assays, automatically selects probes and PCR primers, and integrates BLAST and CLUSTAL sequence alignment capabilities. OMP uses a standardized architecture, which allows it to accept deferent input and output data structures and to combine modules in a deployable fashion. OMP has been successfully commercialized and shown to reduce the development time and improve the reliability of any process involving Oligonucleotide hybridization such as multiplex PCR, DNA sequencing, SNP detection assays, mRNA expression profiling, and a variety of chip arrays. This proposal focuses on the expansion of OMP capability to design probes and primers that contain modified nucleotides, fluorophore labels and hybridize in the presence of buffer additives. This will enable nucleic acid based diagnostic applications that utilize these modifications to enhance sensitivity, specificity, multiplexing and to improve in vivo properties of diagnostic probes. At present, the lack of experimental thermodynamic parameters for modified nucleotides, fluorophores and buffer additives impairs OMP accuracy in predicting hybridization and designing efficient modified oligonucleotides. This proposal will close this gap by providing experimentally measured thermodynamic parameters for most commonly used modifications, fluorophores and buffer additives. These parameters will be incorporated into OMP as well as made publicly available.

描述(申请人提供)：DNA Software Inc.的使命是通过编写企业级模拟软件来支持基因组学领域，该软件结合了最先进的核酸折叠和杂交热力学和动力学知识。为了实现这一目标，DNA Software构建了寡核苷酸建模平台(OMP)，该平台可以准确预测目标二级结构，计算探针杂交热力学，模拟基于DNA或RNA的分析，自动选择探针和PCR引物，并集成BLAST和CLUSTAL序列比对功能。OMP使用标准化的体系结构，允许它接受不同的输入和输出数据结构，并以可部署的方式组合模块。OMP已经成功地商业化，并被证明可以缩短开发时间并提高涉及寡核苷酸杂交的任何过程的可靠性，如多重PCR、DNA测序、SNP检测、mRNA表达谱分析和各种芯片阵列。这项提议的重点是扩大OMP的能力，以设计包含修饰核苷酸、荧光团标记的探针和引物，并在存在缓冲添加剂的情况下进行杂交。这将使基于核酸的诊断应用能够利用这些修饰来提高灵敏度、特异度、多重并改善诊断探针的体内性质。目前，缺乏修饰核苷酸、荧光团和缓冲添加剂的实验热力学参数，影响了OMP预测杂交和设计高效修饰寡核苷酸的准确性。这项提议将通过为最常用的改性剂、荧光团和缓冲添加剂提供实验测量的热力学参数来缩小这一差距。这些参数将被合并到OMP中并公开提供。