马志;张峰;张慧晓;杨威;

• 1:大连海洋大学农业部北方海水增养殖重点实验室

摘要：

应用分子动力学方法研究了人类miRNA 3'末端3碱基与PAZ功能域的结合模式,并采用线性相互作用能方法计算miRNA 3'末端片段与PAZ之间的结合自由能。结果表明:miRNA 3'末端碱基组成决定了其和PAZ功能域的结合模式以及结合自由能,UGU与PAZ的结合最为稳定,结合自由能为-37.248kJ/mol,而CGA与PAZ的结合情况相对不太稳定,结合自由能为-5.418 kJ/mol;miRNA 3'端与PAZ的结合自由能与其在人类miRNA基因中的分布频率存在一定的相关性,UGU在人类基因中占6.768%,而CGA仅占0.414%。本研究结果可为进一步研究miRNA与Argonaute蛋白的相互作用以及对人类疾病防治和生物进化探索提供重要信息。

关键词： miRNA;PAZ功能域;分子动力学模拟;线性自由能

Abstract: The binding model of the human miRNA with the PAZ domain was studied by molecular dynamics,and binding free energies of the miRNA-PAZ complexes were calculated via linear interaction energy(LIE).The analyses revealed that the binding formation of the miRNA with the PAZ domain and the binding free energies of the complexes were depended on the base composition of the 3' end fragment,with the stable binding of UGU to PAZ at the binding free energy of-37.248 kJ/mol,while the binding free energy between CGA and PAZ was found to be-5.418 kJ/mol.Simultaneously,the binding free energies were also found associated with distribution frequency of the miRNA gene,UGU accounting for 6.768%,and CGA accounting for 0.414%.The findings provide information with understanding of the interactions between miRNAs and Ago,the human diseases,and the biological evolution.

Keywords: miRNA;PAZ domain;molecular dynamics simulation;linear interaction energy

基金项目: 国家自然科学基金资助项目(30471323)

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