Demonstration of a Universal Surface DNA Computer

1. Demonstration of a Universal Surface DNA Computer Xingping Su and Lloyd M. Smith* Nucleic Acids Res. 32, 3115-3123 (2004) August 3, 2004 Summarized by Ji-Yoon Park

2. Abstract • Concept of universal Turing machine • Abstract definition of a general purpose computer • General purpose (universal) computer • can compute anything that is computable • any computer can simulate Boolean logic circuits of any complexity • Simulating Boolean logic circuits • The NOR gate: universal gate in Boolean logic gate • Any other logic gate can be built from it alone • Universal nature of surface DNA computing model

3. Computational Complexity (1/2) • In computational complexity theory • the class of NP-complete • A subset of the universal class • Boneh et al. (1996): theoretically solve beyond NP class • Winfree (2000): self assembly/ theoretically & experimentally • Benenson et al. (2001): only read/ less powerful than universal TM • Stojanovic & Stefanovic (2003) : deoxyribozyme-based logic gated & automata/ non-universality • Smith group’s work • Liu et al. (2000): surface-based computer • Frutos et al. (1997): multiple-word encoding • Cai et al. (1997): surface DNA computing model for Boolean logic circuits • In this paper… • Surface DNA computing model to simulate a Boolean logic circuits

4. Computational Complexity (2/2) • P-complete - a set of decision problems - useful in the analysis of which problems can be efficiently solved on parallel computers

5. NOR gate is “universal” – Continuous input

6. Sequences of the DNA encoding

7. Word & Word Complement

8. Experimental Section 1. Sequence design of DNAs and DNA/LNA chimeras 2. DNA attachment 3. Melting analysis 4. Hybridization/ Ligation/ Polymerase extension 5. Efficiency of ligase & computation

9. X1=F, X2=F, X3(X)= T or F X1, X2 Complements & hybridization Ligation Melting Polymerase extension X4=T Ligation X4=F After NOR gate computation X1=T, X2=T complements & hybridization & extension After OR gate computation NOT gate Continuous input X3=F, X4=F

10. NOR gate is “universal” – Non-continuous input

11. X1=T, X3=T complements of LNA/DNA chimera X1=T, X3=T complements of regular DNA Polymerase extension & X4=T X4=F, Polymerase extension Non-continuous input NOR gate computation MARK Operation of OR gate After OR gate computation

12. Circuit Computations After OR gate FT complement to X5=T After NOR gate FT complement to X4=T After NOR gate FT complement to X4=F After NOR gate FT complement to X5=F

13. Overall Computation Efficiency

14. Sequence design of DNAs & DNA/LNA chimeras

15. Deep VentR (exo-) DNA Polymerase • Genetically engineered to eliminate the 3´→ 5´ proofreading exonuclease activity associated with Deep Vent DNA Polymerase • More stable than Vent (exo-) DNA Polymerase - with a half-life of 23 hours at 95°C and 8 hours at 100°C • Both Deep Vent (exo-) & Vent (exo-) DNA Polymerase - suitable for primer extensions - high temperature (72°C) DNA sequencing

16. Summary of Deep VentR (exo-) DNA Polymerase

17. Discussion • A Boolean logic NOR gate • Using the surface computing paradigm • One of universal gate in Boolean logic • LNA/DNA chimera • Block polymerase activity & actual computation • LNA: positional preference - in the interaction of the LNA-modified primer & DNA polymerase • MARK & Append-Marked operation - without any modification