ﻻ يوجد ملخص باللغة العربية
DNA surface-hybridization biosensors utilize the selective hybridization of target sequences in solution to surface-immobilized probes. In this process, the target is usually assumed to be in excess, so that its concentration does not significantly vary while hybridizing to the surface-bound probes. If the target is initially at low concentrations and/or if the number of probes is very large and have high affinity for the target, the DNA in solution may get depleted. In this paper we analyze the equilibrium and kinetics of hybridization of DNA biosensors in the case of strong target depletion, by extending the Langmuir adsorption model. We focus, in particular, on the detection of a small amount of a single-nucleotide mutant sequence (concentration $c_2$) in a solution, which differs by one or more nucleotides from an abundant wild-type sequence (concentration $c_1 gg c_2$). We show that depletion can give rise to a strongly-enhanced sensitivity of the biosensors. Using representative values of rate constants and hybridization free energies, we find that in the depletion regime one could detect relative concentrations $c_2/c_1$ that are up to three orders of magnitude smaller than in the conventional approach. The kinetics is surprisingly rich, and exhibits a non-monotonic adsorption with no counterpart in the no-depletion case. Finally, we show that, alongside enhanced detection sensitivity, this approach offers the possibility of sample enrichment, by substantially increasing the relative amount of the mutant over the wild-type sequence.
We study a protein-DNA target search model with explicit DNA dynamics applicable to in vitro experiments. We show that the DNA dynamics plays a crucial role for the effectiveness of protein jumps between sites distant along the DNA contour but close
Test experiments of hybridization in DNA microarrays show systematic deviations from the equilibrium isotherms. We argue that these deviations are due to the presence of a partially hybridized long-lived state, which we include in a kinetic model. Ex
Quantifying interactions in DNA microarrays is of central importance for a better understanding of their functioning. Hybridization thermodynamics for nucleic acid strands in aqueous solution can be described by the so-called nearest-neighbor model,
The problem of DNA-DNA interaction mediated by divalent counterions is studied using computer simulation. Although divalent counterions cannot condense free DNA molecules in solution, we show that if DNA configurational entropy is restricted, divalen
The effective DNA-DNA interaction force is calculated by computer simulations with explicit tetravalent counterions and monovalent salt. For overcharged DNA molecules, the interaction force shows a double-minimum structure. The positions and depths o