用于寡核苷酸二级结构预测的热力学数据库研究进展

刘哲言,屈武斌,张成岗

( 军事医学科学院放射与辐射医学研究所,蛋白质组学国家重点实验室, 全军军事认知与心理卫生研究中心,北京 100850 )



摘要:

基于核酸分子杂交的生物技术(如PCR)在病原微生物检测、临床诊断等诸多领域中应用广泛,此类技术的可靠性在于寡核苷酸分子与其靶点结合的高稳定性与特异性,而精确预测寡核苷酸与靶分子结合的二级结构是分析其稳定性与特异性的关键。其中,基于热力学的最近邻模型是寡核苷酸二级结构预测最为可靠的计算方法,但其精确性强烈依赖于精确的热力学参数。由于寡核苷酸分子二级结构的复杂性,除了完美匹配外,还需要错配、内环、膨胀环、末端摇摆、CNG重复、GU摆动等特殊结构的热力学数据。本文综述了近年来用于寡核苷酸二级结构预测的有效热力学数据库及相关计算方法,并指出当前热力学数据库的局限及未来发展方向。

关键词:  寡核苷酸二级结构  热力学数据库  热力学计算

DOI：10.3969/j.issn.1672-5565.2014.03.08

分类号:Q522

基金项目:国家自然科学基金课题(2,7, 1,0, 31371345)；国家重点基础研究发展计划(973计划)课题(2012CB518200)；蛋白质组学国家重点实验室自主研究课题(SKLP-O201104, SKLP-K201004, SKLP-O201002) 资助。



Research progress of the thermodynamic database for oligonucleotide secondary structure prediction

LIU Zheyan, QU Wubin, ZHANG Chenggang

(Beijing Institute of Radiation Medicine, State Key Laboratory of Proteomics, Cognitive and Mental Health Research Center, Beijing 100850, China)

Abstract:

The nucleotide hybridization based molecular biological technologies like PCR have been widely used in many fields, such as pathogenic microorganism detection, clinical diagnosis. And the accurate prediction of secondary structures between oligonucleotide and its binding sites is the key to these technologies. The Nearest-Neighbor Model based on thermodynamics is the most accurate method to predict oligonucleotide secondary structure, and the precision mainly depends on the thermodynamic parameters. Meanwhile, the diversity of secondary structure requires different thermodynamic parameters for different motifs, including perfect matches, mismatches, internal loops, bulge loops, dangling ends, CNG repeats, and GU wobble base pairs. Therefore, this review summarized the current parameter sets available for oligonucleotide secondary structure prediction. We also pointed out the limitations and future development directions of the thermodynamic database.

Key words:  Oligonucleotide secondary structure  Thermodynamic database  Thermodynamic calculation