PNA-mediated whiplash PCR
Abstract
In Whiplash PCR( WPCR), autonomous molecular computation is achieved by the recursive, self-directed polymerase extension of a mixture of DNA hairpins. A barrier confronting efficient implementation, however, is a systematic tendency for encoded molecules towards backhybridization, a simple form of self-inhibition. In order to examine this effect, the length distribution of extended strands over the course of the reaction is examined by modeling the process of recursive extension as a Markov chain. The extension efficiency per polymerase encounter of WPCRi s then discussed within the framework of a statistical thermodynamic model. The efficiency predicted by this model is consistent with the premature halting of computation reported in a recent in vitro WPCRimp lementation. The predicted scaling behavior also indicates that completion times are long enough to render WPCR-based massive parallelism infeasible. A modified architecture, PNA-mediated WPCR (PWPCR) is then proposed in which the formation of backhybridized structures is inhibited by targeted PNA2/DNA triplex formation. The efficiency of PWPCRis discussed, using a modified form of the model developed for WPCR. Application of PWPCR is predicted to result in an increase in computational efficiency sufficient to allow the implementation of autonomous molecular computation on a massive scale.
Publication Title
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Recommended Citation
Rose, J., Deaton, R., Hagiya, M., & Suyama, A. (2002). PNA-mediated whiplash PCR. Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), 104-116. https://doi.org/10.1007/3-540-48017-x_10
