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Demonstration of a Universal Surface DNA Computer August 3, 2004 Summarized by Ji-Yoon Park Xingping Su and Lloyd M. Smith* Nucleic Acids Res. 32, 3115-3123 (2004) Slide 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 Slide 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 groups 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 Slide 4 P-complete - a set of decision problemsdecision problems - useful in the analysis of which problems can be efficiently solved on parallel computers Computational Complexity (2/2) Slide 5 NOR gate is universal Continuous input Slide 6 Sequences of the DNA encoding Slide 7 Word & Word Complement Slide 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 Slide 9 X1=F, X2=F, X3(X)= T or F X1, X2 Complements & hybridization LigationMelting Polymerase extension X4=T X1=T, X2=T complements & hybridization & extension Ligation X4=F After NOR gate computation After OR gate computation X3=F, X4=F NOT gate Continuous input Slide 10 NOR gate is universal Non-continuous input Slide 11 X1=T, X3=T complements of LNA/DNA chimera Polymerase extension & X4=T X1=T, X3=T complements of regular DNA X4=F, Polymerase extension NOR gate computation MARK Operation of OR gate After OR gate computation Non-continuous input Slide 12 Circuit Computations After NOR gate FT complement to X4=T After OR gate FT complement to X5=T After NOR gate FT complement to X5=F After NOR gate FT complement to X4=F Slide 13 Overall Computation Efficiency Slide 14 Sequence design of DNAs & DNA/LNA chimeras Slide 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 95C and 8 hours at 100C Both Deep Vent (exo-) & Vent (exo-) DNA Polymerase - suitable for primer extensions - high temperature (72C) DNA sequencing Slide 16 Summary of Deep VentR (exo-) DNA Polymerase Slide 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