The fidelity of annealing-ligation: A theoretical analysis


Understanding the nature of the error propagation through successive biosteps is critical to modeling the overall fidelity of computational DNA architectures. In this work, the fidelity of the compound biostep annealing-ligation is discussed in the limit of zero dissociation, within the framework of a simple statistical thermodynamic model. For simplicity, a DNA ligase of ideal infidelity is assumed, with its error behavior taken as bounding that of real DNA ligases. The derived expression for the fidelity of annealing-ligation indicates that the error coupling is both strong and dependent on sequence. Estimates of the fidelities of annealing and annealing-ligation have also been calculated for various encodings of Adleman's graph, assuming a staggered zipper model of duplex formation. Results indicate the necessity of including information regarding the specific free energies and/or occupancies of accessible duplex states, in addition to information based purely on sequence comparison.

Publication Title

Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)