Effect of single central base pair mismatch on the conformation and stability of surface immobilized DNA: molecular...

We combine molecular dynamics simulations and relative free energy calculation to investigate how single central base mismatch influence the conformation and stability of surface immobilized DNA. For comparison purpose, molecular dynamics simulations have been performed on a central mismatched duplex and the corresponding perfectly matched duplex, respectively. Simulations have been conducted with the generalized Born model. The relative free energy differences of the two systems suggest the single base-pair mismatch may lower the stability of DNA as expectation. The result obtained from the structural analysis shows the average conformations of the two DNA duplexes resemble the B-form, which suggests the central base pair mismatch has little effect on the overall conformation of DNA. Furthermore, our result shows the fluctuation of the perfectly matched duplex is obviously larger than that of the central base pair mismatched duplex. This study gives us a new atomic-level insight into DNA probe-target interaction on the surface. The results presented here will also aid in the design of DNA microarrays for single nucleotide polymorphisms screening.