Modelling DNA-strand displacement reactions in the presence of base-pair mismatches

A simple thermodynamic model, which is capable of quantitatively describing the kinetics of strand displacement reactions in the presence of base-pair mismatches, using a minimal set of parameters.

SDmismatches.py

solves first passage model for:

  • single invader mismatches
  • double invader mismatches
  • single incumbent mismatches

input:

  • mismatch position
  • toehold length
  • displacement length
  • energy parameters dGBP,dGp,dGBM,dGassoc,dGMM
  • branch migration rate
  • concentration
  • mismatch mode (single/double invader, single incumbent)
  • optional second mismatch
  • optional second toehold (handle with care)
  • output option

returns:

if output = 1 (preset)

  • inverse of mean first passage time

if output = 2:

  • inverse of mean first passage time
  • first order rate constant
  • second order rate constant
  • threshold concentration

if output = 3:

  • k1 forward (second order rate constant for toehold binding)
  • k1 backward (first order rate constant for toehold unbinding)
  • k2 (first order rate constant for full displacement)

Demo

01 basic functions

calculates mean-first-passage-time and plots mismatch position dependence for:

  • single invader-target mismatches
  • double invader-target mismatches
  • single incumbent-target mismatches

02 model fitting

uses measured data to perform a fit for:

  • energy parameters
  • branch migration rate constant

03 predictions

compares measured data to a prediction using the parameters obtained in 02 for:

  • incumbent-target mismatches
  • double invader-target mismatches

04 Concentration dependence (demo for output option 2)

The overall rate constant is seprated into a second- and a first-order contribution:

  • concentration dependence

05 DNA network (demo for output option 3)

The overall rate constant is seprated into three rate constants to set up a system of ordinary differential equations:

  • pulse generation using a DNA network

References

Irmisch, P.; Ouldridge, T. E.; Seidel, R. Modeling DNA-Strand Displacement Reactions in the Presence of Base-Pair Mismatches. J. Am. Chem. Soc. 2020, 142, 11451−11463. https://doi.org/10.1021/jacs.0c03105