Sabri Mohamad Zulkeflee, Abdul Hamid Azzmer Azzar, Sayed Hitam Sharifah Mariam, Abdul Rahim Mohd Zulkhairi
Bioengineering Section, Universiti Kuala Lumpur Malaysian Institute of Chemical and Bioengineering Technology (UniKL MICET), Lot 1988, Bandar Vendor Taboh Naning, 78000 Alor Gajah, Melaka, Malaysia.
Department of Biotechnology, Kulliyyah of Science, International Islamic University Malaysia (IIUM), Bandar Indera Mahkota, 25200 Kuantan, Pahang, Malaysia.
Adv Bioinformatics. 2019 Jun 26;2019:6912914. doi: 10.1155/2019/6912914. eCollection 2019.
Aptamer has been long studied as a substitute of antibodies for many purposes. However, due to the exceeded length of the aptamers obtained , difficulties arise in its manipulation during its molecular conjugation on the matrix surfaces. Current study focuses on computational improvement for aptamers screening of hepatitis B surface antigen (HBsAg) through optimization of the length sequences obtained from SELEX. Three original aptamers with affinity against HBsAg were truncated into five short hairpin structured aptamers and their affinity against HBsAg was thoroughly studied by molecular docking, molecular dynamics (MD) simulation, and Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) method. The result shows that truncated aptamers binding on HBsAg "a" determinant region are stabilized by the dynamic H-bond formation between the active binding residues and nucleotides. Amino acids residues with the highest hydrogen bonds hydrogen bond interactions with all five aptamers were determined as the active binding residues and further characterized. The computational prediction of complexes binding will include validations through experimental assays in future studies. Current study will improve the current aptamers by minimizing the aptamer length for its easy manipulation.
适配体作为抗体的替代品已被广泛研究用于多种目的。然而，由于所获得的适配体长度过长，在将其分子偶联到基质表面的过程中操作起来存在困难。当前的研究聚焦于通过优化从指数富集的配体系统进化（SELEX）获得的长度序列，对乙肝表面抗原（HBsAg）的适配体筛选进行计算优化。将三种对HBsAg具有亲和力的原始适配体截短为五种短发夹结构的适配体，并通过分子对接、分子动力学（MD）模拟和分子力学泊松-玻尔兹曼表面积（MMPBSA）方法深入研究了它们对HBsAg的亲和力。结果表明，截短的适配体与HBsAg“a”决定簇区域的结合通过活性结合残基与核苷酸之间动态形成的氢键得以稳定。确定了与所有五种适配体具有最高氢键相互作用的氨基酸残基为活性结合残基并进一步进行了表征。复合物结合的计算预测在未来研究中将通过实验分析进行验证。当前的研究将通过最小化适配体长度以方便操作来改进现有的适配体。
