Study On Nucleosome Dynamics

In eukaryotic organism,147bp of DNA is organized in 1.67 left-handed superhelical turns around an octamer forming nucleosome which is the repeating unit of chromatin fiber. Nucleosome dynamics, one of the core areas of histone protein research projects, is largely concerned with the interaction between DNA and histone octamer and properties of the formation of nucleosome complex. It is of eminent importance, for this is the venue on which the biomanufacturing such as assembly of DNA and proteins are played out. Moreover, the principle of the interaction between DNA and protein is also a pressing problem which must be deal with in the design process of microfluidic chips and biochips. Thus the main research contents in this paper are of special interest to the study of biology microfluidic chips.Based on the interdisciplinary research from the dynamics of mechanical system, various of multiscale simulations are presented to investigate some important influencing factors and dynamic properties in the formation of the nucleosome including DNA wrapping and its folding processes. The preliminary works on our study are as follows:Multiscale modeling of nucleosome dynamicsChromatin fiber are formed after several heirarchical organization of DNA and its basic unit is nucleosome. Generally, a nucleosome includes of a histone octamer and DNA with negative charge which winds around histone octamer with positive charge in left-handed superhelical turns. In this paper, the stretching potential, bending potential and tensional potential are investigated in details based on bead-on-spring model for DNA, homogeneous isotropic bead model for octamer and the folding process of DNA around nucleosome. The numerical models for nucleosome are given here, a series of control equation for the dynamic systems of nucleosome under different influencing factors such as hydraulic force, bending potential and volume effect are also obtained.Multiscale algorithms for nucleosome dynamicsIt is of great significance to develop multiscale algorithms in studying the folding processes of DNA into nucleosome and the multiple-level transition from nucleosome to chromatin fiber. Molecular dynamic simulation method are used in the paper to investigate single nucleosome dynamics, superhelical DNA movement and some of the important properties of histone tails. Moreover, the interaction between DNA and histone octamer in the formation of nucleosome are studied by Brownian dynamics method. Further, Monte Carlo method are presented here to investigate the condense process of multi nucleosomes into chromain fiber. After simulations above some of the parameters obtained are mapped to coarse grain model of next simulation level to perform the multiscale simulation for nucleosome dynamics.A novel multicale simulation method supporting multi-core parallel computation is proposed here to provide a good solution for multiscale coupling and translating problems between different folding level of nucleosome when many parameters are changing at the same time to study the nucleosome dynamics.Software for nucleosome dynamics simulationVisualization software of nucleosome dynamics simulations under different influencing parameters has been developed based on several versions of nucleosome dynamics simulation software published by our lab. It can act powerfully upon analyzing the stretching and wrapping processes of the complex of nucleosome, histone and DNA. There are three building modules and they are nucleosome dynamics module without external influencing factors, nucleosome dynamics module with external influencing factors and multiscale nucleosome dynamic module respectively. Not only can it make a fast improvement in simulation speed but also the property parameters obtained from out results in the paper are consistent with those gained from all atom methods. Simulations of the formation process of nucleosomeThe wrapping processes of single nucleosome and the formation process of chromatin fiber under confinement are presented here. The interaction between DNA and histone and the properties of nucleosome under hydrodynamic are also investigated in the paper. The results show that the salt concentration has a great effect on the wrapping process of DNA around histone octamer. The wrapping process can only happen under moderate salt concentration. When the system is in a state of low salt concentration, only part of DNA can wrap around the histone. When the system is in a state of high salt concentration, little wrapping process can be seen since the interaction between DNA and histone is not strong enough.Simulation of nucleosome stretchingThe chromatin fiber may be in an unfolding state before the fundamental processes of transcription and replication. Meanwhile the histone octamer can be separated from DNA chain which provides the opportunity for the behavior of recombination and repair of the genome. To fully understand the processes of many nucleosomes folding together at the molecular level, weight coefficients of the effect of the interaction between nucleosomes to the solenoid model of chromatin are included in the paper. Moreover the electrical characteristics of the histone HI and histone H5 are also considered to investigate the effects of linker histone on the folding process of nucleosome. The results show that when the force exerted on the ends of DNA are low, only the outer DNA can be separated from histone octamer. Double turns of DNA can be separated from the histone when the force exterted on DNA are increased high enough leaving only the B locus contacted to the histone octamer.Multiscale simulation of nucleosomeMulti nucleosome dynamics, nucleosome confinement dynamics, the interaction between DNA and double histones and the effects of the multivalent of the salt ion to the nucleosome dynamics are investigated using multiscale simulation methods in the paper. After analyzing the interaction between DNA and single histone octamer complex some of the methods used above are extended into analyzing the wrapping process of DNA around double histone octamer complex to reveal the transition process of DNA folding from the first level to the next level. Simulations of the process of separating DNA from histone octamer under external force with and without considering the gene locus on DNA are given in details in the paper. The interaction between long DNA chain and multi histone octamer complex in solvents with multivalent have also been investigated. It is shown that with increasing the value of the valence of ion and Debye length, the interaction between DNA and single histone octamer become weaker and the descent velocity of the attraction potential become larger.A novel simulation method for nucleosome dynamics in solvents with multivalent has been proposed in the paper. The interaction between DNA and histone octamer can not only be affected by salt concentration but also relate to the value of the valence of ions.The results of the research in the paper enriched and optimized foundational problem of multi hierachies in biology science. Meanwhile, the multiscale numeral simulation method proposed and its related programs developed in the paper are also applicable in the multiscale design fields of mechanical engineering.