Molecular Modeling of ssDNA-Salt Interactions

DNA biosensors have been predicted to become an important new feature of medical diagnostics as they allow investigators to assess how DNA sequences interact with surrounding molecules. These devices immobilize one end of DNA aptamers (short strands of naturally occurring nucleotides with the capability to bind to target molecules) to a surface and allow the rest of the strand to interact with target molecules immersed in ionic solutions. The ions in solution impact the structure of the single-stranded DNA, and this impact must be studied to determine the exact interactions between ssDNA and target molecule. Mean-field theory (MFT) calculations have shown that ssDNA immersed in magnesium chloride solutions condense more than ssDNA immersed in sodium chloride solutions. These calculations, however, do not fully account for the charge correlation effects of the divalent ions. Therefore, our sample MFT calculations must be compared to molecular dynamics (MD) simulations to obtain an appropriate correction term for the MFT calculations. MD simulations also have their own disadvantages, including long computational times and inability to capture pH accurately. A unique computational method must subsequently be derived to support the advantages of each method and to eliminate the drawbacks of each. This novel computational method will take the form of a MFT with a charge correlation correction term incorporated from the exact results of the MD simulations. This accurate, reliable method can then be applied to the design of optimally functional biosensors and used to further medical advances.