SimulateReactivity

SimulateReactivity[initialState]⟹reactionMechanism

generates a putative ReactionMechanism that describes the hybridization behavior of the system of nucleic acids or adds reaction rates to known reaction types from in the nucleic acid.

SimulateReactivity[reactionMechanism]⟹reactionMechanism

adds reaction rates to known reaction types from in the nucleic acid reactionMechanism.

Details

SimulateReactivity looks for possible reactions of following types: Folding/Melting, Zipping/Unzipping, Hybridization/Dissociation, StrandInvasion, DuplexInvasion, ToeholdMediatedStrandExchange, ToeholdMediatedDuplexExchange and DualToeholdMediatedDuplexExchange. Exhaustive searching is used for finding reactions, i.e. each species is simulated for first order reactions ane each pair of species is simulated for second order reaction. SimulateKinetics is used to exclude unfavorable structures.
When given a state containing strands with sequences, SimulateReactivity uses Base method by default, which considers Watson-Crick rules to look for valid reactions.
When given a state containing strands without sequences, SimulateReactivity uses Motif method, which considers motif matching to find possible products and use kinetic simulation to determine strong reactions.
Theoretical polymerization can be avoided by setting the Depth option to a small number. Theoretical polymerization can also be excluded by turning on PrunPercentage option.
When a temperature is given, SimulateReactivity will calculate reaction rates with KineticRates function.
Rate for Folding is considered dependent on temperature and monovalent salt concentration as described by Bonnet, G., Krichevsky, O., & Libchaber, A. (1998) in Object[Report,Literature,"id:E8zoYvNkERq5"]: "Kinetics of conformational fluctuations in DNA hairpin-loops." Proceedings of the National Academy of Sciences, 95(15), 8602-8606. The folding rate is fitted by using the kinetics data as a function of 1000/T (K^-1) and monovalent salt concentration (Molar) as described in Object[Analysis,Fit,"id:AEqRl9Kz9YKw"].
Rate for Hybridization is dependent on monovalent salt concentration as decribed by James G. Wetmur (1991) in Object[Report,Literature,"id:wqW9BP7kDBKV"]: "DNA probes: applications of the principles of nucleic acid hybridization." Critical reviews in biochemistry and molecular biology, 26(3-4), 227-259. In the range of interest ([Na+] >= 0.25 Molar), the hybridization rate is given by Kon = {4.35*Log10[Na+]+3.5}*10^5. When salt concentration is below 0.25 Molar, hybridization starts becoming more stringent as only perfectly matched hybrids will be stable, thus the rate drops according to decreasing salt concentration. Temperature also plays a vital role in hybridization rate as described by Chunlai Chen, et al (2007) in Object[Report,Literature,"id:BYDOjvGNmwNr"]: "Influence of secondary structure on kinetics and reaction mechanism of DNA hybridization" Nucleic acids research, 35(9), 2875-2884. Log[Kon] was fitted as a function of 1/RT (mol*K/cal) where R is the ideal gas constant, the fitted function as described in Object[Analysis,Fit,"id:01G6nvw7veVE"] is used to predict the hybridization rate given the temperature.
Rate for ToeholdMediatedStrandExchange uses kinetic data described in Object[Report, Literature, "id:XnlV5jmalqMZ"] : B. M. Frezza "Orchestration of molecular information through higher order chemical recognition." (2010). This data was log-normalized and fitted to compute kinetic rates as function of the activation energy normalized by the Temperature and Boltzmann factor in Object[Analysis, Fit, "id:dORYzZJKnMd5"] for 3' toehold and Object[Analysis, Fit, "id:P5ZnEjdL4nkE"] for 5' toehold.
Rate for ToeholdMediatedDuplexExchange uses kinetic data described in Object[Report, Literature, "id:XnlV5jmalqMZ"] : B. M. Frezza "Orchestration of molecular information through higher order chemical recognition." (2010).
Rate for DualToeholdMediatedDuplexExchange is similar to ToeholdMediatedStrandExchange but with a different AnalyzeFit object as in Object[Analysis,Fit,"id:mnk9jORoVr9w"].
Rate for StrandInvasion uses kinetic data described in: L. P. Reynaldo et al in Object[Report,Literature,"id:7X104vnRe98J"]: "The kinetics of oligonucleotide replacements." J. Mol. Biol. 297 (2000): 511-520. For strand invasion mediated by the sequential displacement pathway, related kinetic data was fitted as a function of the number of displaced bonds and the temperature in Object[Analysis,Fit,"id:Vrbp1jKDZZzx"]. For strand invasion mediated by the dissociative pathway, related kinetic data was fitted as a function of the number of dissociated bonds and the temperature in Object[Analysis,Fit,"id:9RdZXv1W7E9L"].
Rate for DuplexInvasion is as described in Object[Report, Literature, "id:XnlV5jmalqMZ"] : B. M. Frezza "Orchestration of molecular information through higher order chemical recognition." (2010), signal measured was not significant. Thus the duplex invasion rate is set to be 0/Molar/Second.

Input

Output

General Options

Examples

Basic Examples (5)

Initial state can be specified as a list of species without concentration:

Initial state can be specified as a list of rules:

Generate a ReactionMechanism from sequence interactions:

Generate a ReactionMechanism from motif interactions:

Add reaction rates to the input ReactionMechanism:

Options (19)

Depth (2)

By default Depth is 5, which first finds the products from input species then makes these products as reactants to find more reactions:

Set Depth to 1 so that only the initial input structures are involved in reactions:

FoldingDepth (1)

Set FoldingDepth to 1 so that structures only fold once at each step:

HybridizationDepth (1)

Set HybridizationDepth to 1 so that structures only hybridize once at each step:

InterStrandFolding (1)

Turn off InterStrandFolding so that hybridized structure does not further fold among strands:

IntraStrandFolding (1)

Turn off IntraStrandFolding so that hybridized structure does not further fold within strands:

MaxMismatch (2)

By default, MaxMismatch is set to 0, i.e. no mismatch in product sturcuture allowed:

Allows 1 base mismatch to find more reactions with products having mismatch:

Method (2)

Default method is Base for explicit sequences to find reactions with respect to base pairing rules:

Use Motif method on explicit sequences to focus on motif level interactions:

MinFoldLevel (1)

Use MinFoldLevel to specify minimum number of consecutive bases for folding:

MinPairLevel (1)

Use MinPairLevel to specify minimum number of consecutve bases for pairing:

MinPieceSize (1)

Specify minimum number of consecutive paired bases required in a structure containing mismatches:

PrunePercentage (1)

Turn PrunPercentage to 0 Percent so that all the reactions can be found:

Reactions (1)

Use Reactions option to find specific reactions instead of all possible reactions:

Temperature (1)

Specify temperature as Null to keep reaction rate symbolic:

Template (2)

Inherit options from existing Object[Simulation,ReactionMechanism] object reference:

Inherit options from existing Object[Simulation,ReactionMechanism] object:

Time (1)

Set simulation time (only when using motif matching):

Messages (2)

InconsistentReactants (1)

Structures specified in Reactions option must exist in input:

UnsupportedMethod (1)

Cannot use Base method on degenerate sequences:

Applications (2)

Generate a ReactionMechanism from initial state then call SimulateEquilibrium to simulate the equilibrium state of the ReactionMechanism:

Instead of simulate equilibrium state directly, you can also call SimulateKinetics to simulate the kinetic trajectory of the ReactionMechanism to see concentration changes with respect to time: