PNA-mediated Whiplash PCR

In Whiplash PCR WPCR autonomous molecular compu tation is achieved by the recursive self directed polymerase extension of a mixture of DNA hairpins A barrier confronting e cient implementa tion however is a systematic tendency for encoded molecules towards backhybridization a simple form of self inhibition In order to examine this e ect 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 e ciency per polymerase encounter of WPCR is then discussed within the framework of a statistical ther modynamic model The e ciency predicted by this model is consistent with the premature halting of computation reported in a recent in vitro WPCR implementation The predicted scaling behavior also indicates that completion times are long enough to render WPCR based massive parallelism infeasible A modi ed architecture PNA mediated WPCR PWPCR is then proposed in which the formation of backhybridized structures is inhibited by targeted PNA DNA triplex formation The e ciency of PWPCR is discussed using a modi ed form of the model developed for WPCR Application of PWPCR is predicted to result in an increase in computational e ciency su cient to allow the implemen tation of autonomous molecular computation on a massive scale