A validation strategy for in silico generated aptamers

Abstract: 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 aptamers, produced in silico by using free software. The procedure 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 energy. Step c. employs a complex network approach (Proteotronics) to characterize the electrical properties of the aptamers and the ligand-receptor complexes. The test-bed is represented by a group of anti- Angiopoietin-2 aptamers. 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, while our results show a good agreement with the known measurements. The devised procedure is not aptamer-specific and, integrating structure production with structure selection, candidates itself as a quite complete theoretical approach for aptamer selection.