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.
A validation strategy for in silico generated aptamers
alfinito, eMembro del Collaboration Group
;cataldo,rMembro del Collaboration Group
;
2018
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 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
