6533b86dfe1ef96bd12ca99d
RESEARCH PRODUCT
Design and experimental validation of a generic model for combinatorial assembly of DNA tiles into 1D-structures.
Denis PomponAude LaisneEric Lesniewskasubject
education.field_of_studyBase SequenceModels GeneticSystems biologyDesign of experimentsPopulationMolecular Sequence DataBiophysicsStructure (category theory)Process (computing)Reproducibility of ResultsNanotechnologyDNABiologyBiochemistryCharacterization (materials science)Synthetic biologyKineticsDrug DesignCombinatorial Chemistry TechniquesComputer SimulationMacroeducationBiological systemMolecular Biologydescription
Abstract Background Quantitative modeling of the self-assembly of DNA tiles leading either to defined end-products or distribution of biopolymers is of practical importance for biotechnology and synthetic biology. Methods The combinatorial process describing tile assembly was implemented into a generic algorithm allowing quantitative description of the population of significant species accumulating during the reaction course. Experimental formation and characterization by optical and electrophoresis approaches of copolymers resulting from the self-assembly of a limited number of half-complementary tiles were used to define and validate generic rules allowing definition of model parameters. Results Factors controlling the structure and the dynamic of the oligomer population were evidenced for assemblies leading or not to defined end-products. Primary parameters were experimentally determined using rapid mixing experiments. Adjustment of simulations to experimental profiles allowed definition of generic rules for calculation of secondary parameters that take into account macro- and microenvironment of individual hybridization steps. In the case of copolymers, accurate simulation of experimental profiles was achieved for formation of linear assemblies. Conclusions Overall length of species and structure of the DNA regions flanking the hybridization sites are critical parameters for which calculation rules were defined. The computational approach quantitatively predicted the parameters affecting time-course and distribution of accumulating products for different experimental designs. General significance The computational and parameter evaluation procedures designed for the assembly of DNA tiles into large 1D-structures are more generally applicable for the construction of non-DNA polymers by extremities-specific recognition of molecular blocks.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-12-04 | Biochimica et biophysica acta |