A validation strategy for in silico generated aptamers
A validation strategy for in silico generated aptamers
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DOI：
10.1016/j.compbiolchem.2018.09.014
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发表时间：
2018-12-01
影响因子：
3.1
通讯作者：
Alfinito, E.
中科院分区：
文献类型：
--
作者：
Cataldo, R.;Ciriaco, F.;Alfinito, E.
高亲和力适体的选择对于临床和技术应用具有重要意义。提出了一种新的策略来验证一组抗血管生成素-2适体的3D结构的可靠性，这些适体通过使用免费软件在计算机上产生。在以前的文献中，这些适体在体外和计算机上都进行了处理，通过使用与这里提出的方法不同的方法，最后用SPS实验进行了测试。计算结果与实验结果不一致。产生每个候选适体的大量构象; B.在所述受体上的刚性对接; c.产品的拓扑和电气特性。步骤a.和B.基于“有效亲和力”的分布，即构象能和对接能的总和，允许配体-受体复合物的全局结合得分。步骤c.采用复杂网络方法（Proteotronics）来表征适体和配体-受体复合物的电性质。最后，对结果进行了讨论，并与文献中相同的适体。计算预测与已知的实验测量结果吻合良好。
The selection of high-affinity aptamers is of paramount interest for clinical and technological applications. A novel strategy is proposed to validate the reliability of the 3D structures of a group of anti- Angiopoietin-2 aptamers, produced in silico by using free software. In a previous literature these aptamers were processed both in vitro and in silico, by using an approach different from that here presented, and finally tested with a SPS experiment. Computational expectations and experimental outcomes did not agree.The procedure here proposed consists of three steps: a. the production of a large set of conformations for each candidate aptamer; b. the rigid docking upon the receptor; c. the topological and electrical characterization of the products. Steps a. and b. allow a global binding score of the ligand-receptor complexes based on the distribution of the "effective affinity", i.e. the sum of the conformational and the docking energies. Step c. employs a complex network approach (Proteotronics) to characterize the electrical properties of the aptamers and the ligand-receptor complexes. Finally, the results are discussed and compared with the literature on the same aptamers. The computational predictions are in good agreement with the known experimental measurements.