Single-stranded DNA or RNA molecules (Aptamers) which bind to selected target proteins are in the attention for computational docking studies. With advent of different simulation procedures, the selection of nucleic acid aptamers that binds to proteins tightly and specifically has become efficient. Discovery Studio 3.5 is a modeling and simulation software package for both small and macromolecule study. Firstly a comparative study was carried out to analyze the consistency of the docking score between thrombin and its aptamers from literature studies. A rigid-body docking procedure, ZDOCK which uses Pairwise Shape Complementarity (PSC) function has provided reliable results for thrombin and its aptamers and was consistent with previous study.
Angiopoietin-2 (Ang2) displays its appearance in the change vasculature of human tumors. With aim to introduce computational simulation approach to screen high binding aptamers for angiopoietin-2 (Ang2), we used ZRANK from Discovery studio 3.5 and studied the interactions between Ang2 and its aptamers from literature. Based on ZRANK scores obtained, three high binding affinity aptamers were selected. 189 sequences with two-point mutations were produced from three scrutinized high binding aptamers and simulated with Ang2.
Although ZDOCK and ZRANK set as alternative method to in silico selection of aptamers, the resulted simulation aptamers may prove difficult to adapt for biosensor applications. We therefore attempted to develop selection method for aptamers. Surface plasmon resonance (SPR) biosensor was used to test the binding affinity of high and low ZRANK score Ang2/aptamers. A particular RNA aptamer showed higher binding affinity and SPR response to Ang2 than reported in literature. Using ZRANK scoring function, this is the first study of the in silico selection of aptamers against Ang2.