Construction And Applications Of A Coarse-grained DNA Model

As the carrier of the genetic information and the most important biomacromolecules,DNA has gained great attention from the theoretical,experimental and computational researchers.In present thesis,we study several fundamental problems associated with the thermodynamic behaviors of DNA with the computational method.First,we study the confinement effect on the renaturation and denaturation processes of DNA with a coarse-grained model reported by de Pablo.Then,we construct a coarser model which maps one nucleotide to just one bead.Taking advantage of this model,we investigate the toehold exchange process,the influence of mutation on strand displacement and the formation pathway of branched DNA and the hydrogel network.The contents of this thesis include:1.We study the effects of the cylindrical and spherical confinements on the renaturation and denaturation behaviors with 3SPN model constructed by de Pablo's group.Our simulation reveals that the melting temperature of DNA increases as the confinement size of the tube or sphere decreases.The Tm shift follows a scaling law with the confinement size.The exponential value is 1.323 for cylindrical confinement and 1.754 for spherical confinement.2.We construct a coarse-grained DNA model and a AuNP model and study the experimental catassembly system.We investigate the influences of Au NP and toehold length on the toehold exchange process.Our result quantitatively explains the dependence of the strand displacement reaction on the toehold length in the presence of Au NP.3.Based on the work involving correct catalyst,we also study the impact of SNP on the toehold exchange process.Our results reveal that different mutation positions markedly influence the potential energy surface of strand displacement.It is found that the catassembly reaction can not proceed when mutation happens on the catalyst strand.This result is consistent with the experimental work.4.We study the formation pathway of Y-and X-type branched DNA and the assembled product.Our results reveal that branched DNA is formed arm after arm and the sequence depends on the binding strength of each arm.The formation of the hydrogel network begins with the nucleation growth.Afterwards,the networks gradually grow and occasionally merge.