System and method for propagating information using modified nucleic acids

Abstract

A method is provided for improving a nucleic acid-based molecular computing system comprised of (i) a nucleic acid structure, (ii) at least one polynucleotide displacement molecule that can bind with the nucleic acid structure under hybridizing conditions, and (iii) a clashing polynucleotide molecule that competes with the polynucleotide displacement molecule for binding the nucleic acid structure under the hybridizing conditions The method entails incorporation of chemical modification that inhibits the binding of the clashing molecule and the nucleic acid structure or facilitates the binding of the displacement molecule and the nucleic structure.

What is claimed is: 
     
         1 . A method for improving a nucleic acid-based molecular computing system, comprising
 (A) identifying a computing system comprised of (i) a nucleic acid structure that comprises an incompletely base-paired duplex domain, (ii) at least one polynucleotide displacement molecule that can bind with said nucleic acid structure under hybridizing conditions, such that said nucleic acid structure undergoes a transition in energy state due to a branch migration reaction involving said duplex domain, and (iii) a clashing polynucleotide molecule that competes with said polynucleotide displacement molecule for binding said nucleic acid structure under said conditions but that cannot produce a branch migration reaction involving said duplex domain; then   (B) reconfiguring at least one of said displacement molecule and said nucleic acid structure, respectively, to incorporate a chemical modification relative to a first reference molecule that comprises natural nucleotides and has the same sequence content as said displacement molecule or said nucleic acid structure, as the case may be,   wherein said modification causes binding of said displacement molecule and said nucleic acid structure to have a hybridization free energy, differing from that of a first reference binding between said displacement molecule or said nucleic acid structure and said first reference molecule, such that said branch migration reaction is facilitated relative to said first reference binding; and/or   (C) reconfiguring at least one of said clashing molecule and said nucleic acid structure, respectively, to incorporate a chemical modification relative to a second reference molecule that comprises natural nucleotides and has the same sequence content as said clashing molecule or said nucleic acid structure, as the case may be,   wherein said modification causes binding of said clashing molecule and said nucleic acid structure to have a hybridization free energy, differing from that of a second reference binding between said clashing molecule or said nucleic acid structure and said second reference molecule, such that binding of said clashing molecule is impeded relative to said second reference binding.   
     
     
         2 . The method of  claim 1 , wherein said branch migration reaction is facilitated by:
 increasing a probability of productive reactions in which binding of said nucleic acid structure by said displacement molecule has, by virtue of said chemical modification, a lower hybridization free energy than does a first reference binding reaction; or   
     
     
         3 . The method of  claim 1 , wherein said branch migration reaction is facilitated by:
 reducing a probability of unproductive reactions in which binding of said nucleic acid structure by said clashing molecule has, by virtue of said chemical modification, a higher hybridization free energy than does a second reference binding reaction.   
     
     
         4 . The method of  claim 1 , wherein said nucleic acid structure is part of an enzyme-free, nucleic acid logic gate selected from the group consisting of an AND gate, a NOT gate, an OR gate, a NAND gate, a NOR gate, an XOR gate, and an XNOR gate. 
     
     
         5 . The method of  claim 1 , wherein said chemical modification is selected from the group consisting of (i) replacing the sugar-phosphodiester backbone of said nucleotides with a pseudo-peptide backbone, (ii) modifying the sugar moiety of said nucleotides, and (iii) substituting an analogue for the nitrogenous base of at least one of said nucleotides. 
     
     
         6 . The method of  claim 5 , wherein said chemical modification comprises replacing the sugar-phosphodiester backbone of said nucleotides with a pseudo-peptide backbone into which a guanidinium functional group is incorporated. 
     
     
         7 . The method of  claim 5 , wherein said chemical modification comprises substituting a tricyclic cytosine analogue for the nitrogenous base of at least one of said nucleotides. 
     
     
         8 . The method of  claim 5 , wherein said chemical modification comprises introducing a heteroatom at the 2′-position of said sugar moiety. 
     
     
         9 . The method of  claim 1 , wherein said branch migration reaction comprises a toe-hold-mediated strand displacement. 
     
     
         10 . A nucleic acid-based system for propagating information, the system comprising:
 (A) a nucleic acid structure that comprises an incompletely base-paired duplex domain;   (B) at least one polynucleotide displacement molecule to effect binding with said nucleic acid structure under hybridizing conditions, such that said nucleic acid structure undergoes a transition in energy state due to a branch migration reaction involving said duplex domain; and   (C) at least one polynucleotide clashing molecule capable of binding with said nucleic acid structure under hybridizing conditions, such that said nucleic acid structure and said clashing molecule are bound and prevent the binding of the polynucleotide displacement molecule,   wherein at least one of said displacement molecule and said nucleic acid structure, respectively, has a chemical modification relative to a reference molecule that comprises natural nucleotides and has the same sequence content as said displacement molecule or said nucleic acid structure, as the case may be,   wherein said modification causes said binding to have a hybridization free energy, differing from that of a reference binding between said displacement molecule or said nucleic acid structure and a reference molecule, such that said branch migration reaction is facilitated relative to said reference binding,   and/or   wherein at least one of said clashing molecule and said nucleic acid structure, respectively, has a chemical modification relative to a reference molecule that comprises natural nucleotides and has the same sequence content as said displacement molecule or said nucleic acid structure, as the case may be,   wherein said modification causes said binding to have a hybridization free energy, differing from that of a reference binding between said displacement molecule or said nucleic acid structure and a reference molecule, such that binding of said clashing molecule is impeded relative to said reference binding.   
     
     
         11 . The system of  claim 10 , wherein said nucleic acid structure is part of an enzyme-free, nucleic acid logic gate selected from the group consisting of an AND gate, a NOT gate, an OR gate, a NAND gate, a NOR gate, an XOR gate, and an XNOR gate. 
     
     
         12 . The system of  claim 11 , wherein said system comprises one or more circuits comprised of a plurality of enzyme-free, nucleic acid logic gates. 
     
     
         13 . The system of  claim 10 , wherein said chemical modification is selected from the group consisting of (i) replacing the sugar-phosphodiester backbone of said nucleotides with a pseudo-peptide backbone, (ii) modifying the sugar moiety of said nucleotides, and (iii) substituting an analogue for the nitrogenous base of at least one of said nucleotides. 
     
     
         14 . The system of  claim 13 , wherein said chemical modification comprises replacing the sugar-phosphodiester backbone of said nucleotides with a pseudo-peptide backbone into which a guanidinium functional group is incorporated. 
     
     
         15 . The system of  claim 14 , wherein said chemical modification comprises substituting a tricyclic cytosine analogue for the nitrogenous base of at least one of said nucleotides. 
     
     
         16 . The system of  claim 14 , wherein said chemical modification comprises introducing a heteroatom at the 2′-position of said sugar moiety. 
     
     
         17 . The system of  claim 10 , wherein said branch migration reaction comprises a toe-hold-mediated strand displacement. 
     
     
         18 . A system for propagating information, the system comprising a first molecule, anda second molecule configured to bind with the first molecule, wherein
 (A) at least one of the first molecule or the second molecule, respectively, has a chemical modification relative to a reference molecule that has the same sequence content as the first molecule or the second molecule, as the case may be, and   (B) the modification causes said binding to have a free energy different from that of a reference binding between the reference molecule and the first or second molecule, such that at least one of the following is realized in the system: (i) the probability of a productive binding is raised; and (ii) the probability of an unproductive binding is reduced.   
     
     
         19 . The system of  claim 18 , wherein the productive binding comprises a binding that propagates information, and wherein the unproductive binding comprises a binding that does not propagate information. 
     
     
         20 . The system of  claim 18 , wherein the free energy difference as a result of the modification decreases for the productive binding, and increases for the unproductive binding.