Premium
Integration of multiple computer modeling software programs for characterization of a brain natriuretic peptide sandwich DNA aptamer complex
Author(s) -
Bruno John G.
Publication year - 2019
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.2809
Subject(s) - aptamer , computational biology , complementarity (molecular biology) , binding selectivity , dna , chemistry , rna , epitope , combinatorial chemistry , binding site , docking (animal) , complementarity determining region , biophysics , microbiology and biotechnology , biology , biochemistry , genetics , medicine , antibody , peptide sequence , gene , nursing
Several molecular modeling programs including Pep‐Fold 3, Vienna RNA, RNA Composer, Avogadro, PatchDock, RasMol, and VMD were used to define the three‐dimensional and basic binding characteristics of an extant sandwich DNA aptamer assay complex for human brain natriuretic peptide (BNP). In particular, the theoretical question of demonstrating likely binding of 72 base capture and reporter aptamers to at least two separate “epitopes” or binding sites on the small 32‐amino acid BNP target was addressed, and the data support the existence of separate aptamer binding sites on BNP. The binding model was based on first docking BNP to the capture aptamer based on shape complementarity with PatchDock, followed by docking the capture aptamer‐BNP complex with the reporter aptamer in PatchDock. Although, shape complementarity clearly dominated this binding model and aptamers are known to be somewhat flexible, the model demonstrates hydrogen bond stabilization within each of the two different aptamers and between the aptamers and the BNP target, thus suggesting a strong binding and high affinity sandwich assay that matches the author's former published assay results (Bruno et al., Microchem. J. 2014;115:32‐38) with subpicogram per milliliter sensitivity and good specificity. Other aspects such as capture and reporter aptamer interactions in the absence of BNP are illustrated and suggest means for potentially improving the existing assay by truncating the capture and reporter aptamers where they overlap to further decrease background signal levels.