Simulating DNA hybridization on an amine-functionalized silicon substrate

The ability of DNA biosensors to capture oligonucleotide molecules in solution is of great importance in genetics, medical diagnostics, and drug discovery. The DNA hybridization event in which the probe, which is usually a single-stranded DNA segment covalently immobilized on a functionalized surface via a cross-linker molecule, recognizes the complementary target and forms a stable duplex structure is the basis of highly specific biorecognizing devices. The rate of hybridization depends on the solvent, length of the strands, complexity of the system, and other factors and could be considerably altered by the type of attachment and by the density of the probe on the substrates. Recent experimental investigations have shown that some probes can hybridize directly from bulk solutions. In this computational study, we provide a model for the behavior of these systems choosing cross-linker, probe, and target on the basis of experimental data. MD simulations of the single-stranded DNA fragment 5'-d(TGGC)-3' attached to an allylamine-functionalized Si(111) surface through an oxanine cross-linker in aqueous solution containing the complementary sequence, i.e. 5'-d(CGCCA)-3', are presented. A possible probe-target capture mechanism obtained using explicit solvent and state-of-the-art classical molecular dynamics simulation protocols is described. The hybridization process of the tethered DNA single strand, the intermediate structures appeared during the formation of the double helix, their internal dynamics and their behavior with respect to the substrate are characterized in detail.