Cε3-Cε4蛋白寡核苷酸适配子结合位点的预测与筛选

doi:10.7503/cjcu20180428

高等学校化学学报 ›› 2019, Vol. 40 ›› Issue (1): 83.doi: 10.7503/cjcu20180428

Cε3-Cε4蛋白寡核苷酸适配子结合位点的预测与筛选

刘中成^1,², 刘世芳^1,², 张苏^1,², 杨艳蕾^1,², 李飞^1,², 张楠^1,², 袁欣^1,², 张艳芬^2,³

1. 河北大学药学院, 保定 071002
2. 河北省药物质量分析控制实验室, 保定 071002
3. 河北大学科学技术处, 保定 071002

收稿日期:2018-06-11 出版日期:2019-01-10 发布日期:2018-12-03
作者简介:联系人简介: 张艳芬, 女, 副教授, 主要从事微生物生化药学方面的研究. E-mail: zhangjing@hbu.edu.cn
基金资助:
国家自然科学基金(批准号: 81202338)、河北省自然科学基金(批准号: H2016201121)、河北省高等学校科学技术研究项目(批准号: ZD2017010)和国家级大学生创新创业训练计划项目(批准号: 201610075007, 201710075016)资助.

Structure Prediction and Screening of Oligonucleotide Aptamers Target Cε3-Cε4 Protein^†

LIU Zhongcheng^1,², LIU Shifang^1,², ZHANG Su^1,², YANG Yanlei^1,², LI Fei^1,², ZHANG Nan^1,², YUAN Xin^1,², ZHANG Yanfen^2,^3,^*

1. College of Pharmaceutical Sciences, Hebei University, Baoding 071002, China
2. Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Baoding 071002, China
3. Offices of Science and Technology, Hebei University, Baoding 071002, China

Received:2018-06-11 Online:2019-01-10 Published:2018-12-03
Contact: ZHANG Yanfen
Supported by:
† Supported by the National Natural Science Foundation of China(No.812022338), the Natural Science Foundation of Hebei Province, China(No.H2016201121), the Hebei Provincial Department of Education Key Research Project, China(No.ZD2017010) and the National College Students Innovation and Entrepreneurship Training Program, China(Nos.201610075007, 201710075016 ).

摘要/Abstract

摘要：

采用NPDock程序对Cε3-Cε4蛋白与其核酸适配子A1的结合位点进行了预测与筛选, 筛选出A1与Cε3-Cε4蛋白结合的关键位点. 同时, 根据蛋白与DNA片段复合物结合界面中氨基酸残基和碱基统计分析发现, 结合界面氨基酸富集碱基G能力最强, 富集碱基T和C能力次之. 本文建立了以NPDock程序虚拟对接为基础的高效适配子优化方法, 为相关研究提供了实验参考.

关键词: Cε3-Cε4蛋白;, NPDock程序, 分子对接, 适配子筛选

Abstract:

The prediction and selection of binding sites between aptamers and targets are the key steps in SELEX process, however, the conventional screening process is complicated. As a new convenient screening method, the virtual screening based on computer has widely used in aptamers screening. The nucleic acid-protein dock(NPDock) program was used to predict and screen the binding site of Cε3-Cε4 protein and its aptamer A1 based on their molecular docking, and the key site of binding to Cε3-Cε4 protein was screened. According to the amino acid residues and bases in the binding interface between the protein and the DNA complexes by virtual docking, the results showed that the amino acid in the binding interface is most capable of enriching the base G, followed by the ability of enriching the base T and the base C. An efficient optimization method was established based on NPDock docking, which would provide an experimental reference for related researches.

Key words: Cε3-Cε4 protein ;, Nucleic acid-protein dock program, Molecular docking, Aptamers screening

中图分类号:

O621

TrendMD:

刘中成, 刘世芳, 张苏, 杨艳蕾, 李飞, 张楠, 袁欣, 张艳芬. Cε3-Cε4蛋白寡核苷酸适配子结合位点的预测与筛选. 高等学校化学学报, 2019, 40(1): 83.

LIU Zhongcheng, LIU Shifang, ZHANG Su, YANG Yanlei, LI Fei, ZHANG Nan, YUAN Xin, ZHANG Yanfen. Structure Prediction and Screening of Oligonucleotide Aptamers Target Cε3-Cε4 Protein^†. Chem. J. Chinese Universities, 2019, 40(1): 83.

图/表 11

Fig.1 3D structure of Cε3-Cε4 protein

Table 1 Sequences for DNA aptamers

No.	Sequence(5'-3')	No.	Sequence(5'-3')
1	ACCGACCGT	25	TGTCTTGTCTTTAATGGTATCCACA
2	CCGACCGTGCTGG	26	TGTCTTTAATGGTATCCACA
3	CCGTGCTGG	27	CTTGTCTTTAATGGTATCCACAG
4	CGACCG	28	TTGTCTTTAA
5	ACCGT	29	TGTCTTTAATGGTATCCA
6	GACCGTGCTGGACTC	30	GTCTTTAATGGTATCCA
7	CGTGCTGGACTCTGCCCCG	31	TCTTTAATGGTATCCACAGTATGA
8	GTGCTGGAC	32	CTTTAATGGTATCCACAG
9	GCTGGACTCTGC	33	TTTAA
10	TGGACTCTGCCCCGCTGCCTTGCA	34	TAATGGTA
11	GGACTCTGCCCC	35	ATGGTAT
12	GGACTCTGCC	36	GGTATCC
13	GACTCTGCCCCGCTGCCTTGCATC	37	GTATCCAC
14	ACTCTGCCCCGCTGCCTTGCATCTGT	38	TATCCACAGTA
15	GCCCCGC	39	ATCCACAGTAT
16	GCCCCGCTGC	40	TCCACAGTATGA
17	GCTGCCTTGC	41	CACAGTATG
18	TGCCTTGCA	42	CAGTATG
19	CATCTG	43	GCGAGC
20	TTGCATCTGTCTTGTCTTTAA	44	GCGAGCGTTGC
21	CATCTGTCTTG	45	CGAGCG
22	ATCTGTCTTGTCTTTAAT	46	CGAGCGTTGCG
23	TGTCTTGTCTTTAATGGTATCCA	47	GCGTTGC
24	GTCTTGTCTTTAATGGTATCCACAG	48	CGTTGCG

Fig.2 3D structures prediction of DNA short hairpin(A)—(F) 3D structures of sequences 4, 10, 18, 21, 22, 29 by MMB; (G)—(L) 3D structures of sequences 4, 10, 18, 21, 22, 29 by RNA composer.

Fig.3 3D conformation of DNA short hairpins and Cε3-Cε4 protein interaction predicted by NPDock(A)—(C) 3D visualization of the 4, 18, 21 best scored complex.

Fig.4 Plot illustrating score changes during a simulation

Fig.5 Scoring statistic of DNA fragments and Cε3-Cε4 protein docking results

Table 2 Best sequences of DNA aptamers from docking results

No.	Sequence	Score	No.	Sequence	Score
6	GACCGTGCTGGACTC	4.08	22	ATCTGTCTTGTCTTTAAT	4.17
11	GGACTCTGCCCC	3.87	23	TGTCTTGTCTTTAATGGTATCCA	3.72
12	GGACTCTGCC	4.85	25	TGTCTTGTCTTTAATGGTATCCACA	3.97
20	TTGCATCTGTCTTGTCTTTAA	3.72	31	TCTTTAATGGTATCCACAGTATGA	3.82

Fig.6 Predictions for protein-DNA complexes(A) The site of interaction of sequence 11 protein complex, the purple are the amino acid residues Thr, Ser, Asp, Lys and His. The cyan are the base T, C and G. (B) The site of interaction of sequence 22-protein complex, the purple are the amino acid residues Ala, Arg, Val, Lys, Glu and Arg. The cyan are the base A, T, C and G.

Fig.7 Frequency of amino acid usage at the site of complex interactiona. Thr; b.Arg; c. Ser; d. Gln; e. Lys; f. Val; g. Asp; h. Pro; i. Glu; j. Phe; k. Ala; l. Asn; m. His; n. Ile; o. Leu; p. Met; q. Tyr.

Fig.8 Binding patterns between the amino acid-nucleotide pairs

Fig.9 Distribution of the frequency of the interaction between each of the amino acids and each of the four nucleotides

参考文献 21

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Cε3-Cε4蛋白寡核苷酸适配子结合位点的预测与筛选

Structure Prediction and Screening of Oligonucleotide Aptamers Target Cε3-Cε4 Protein^†

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Cε3-Cε4蛋白寡核苷酸适配子结合位点的预测与筛选

Structure Prediction and Screening of Oligonucleotide Aptamers Target Cε3-Cε4 Protein†

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Structure Prediction and Screening of Oligonucleotide Aptamers Target Cε3-Cε4 Protein^†