Research Of Structure-function Relationship For Two Types Of Gene Regulatory Factors Using Dynamic Correlation Network

The gene regulation studies are mainly focused on finding the regulatory genes and determining the regulatory pathways.However,it remains unkown that the underlying mechanism of how regulator structure changes to obtain biological functions.Most of the regulatory factors are proteins and some are RNAs,which play key roles in the regulation of gene expression.Deciphering the structure-function relationship will help us to understand the mechanism of regulator function and finally to shed light into drug design.Traditional experiment methods are not efficient in studying the structure and biology function,so here we apply molecular dynamic simulation on two types of regulators.The first one is cancer related “reader” TRIM24,which can recognize the histone modification.In order to study the relationship between TRIM24 and modified histone,various systems were designed by mean of molecular dynamic simulations and the simulated trajectories were analyzed to find the distinction at the structure level.Furthermore we used dynamic correlation network and community network to analyze the information transfer in system of H3K23 ac,finally a hypothesis of “synergistic modification induced regulation” was proposed to explain the specific recognition between TRIM24 and modified histone.We also found a shortest pathway between K4 and K23,a unique pathway which has not been found in other systems.The second,we chose Tetrahydrofolate-riboswitch as another research target.There are two types of THF-riboswitch,one of which can bind a THF at 3WJ site and the other can bind two THF at 3WJ and PK site respectively.By constructing different systmes we also carried out molecular dynamic simulations.After structure analysis,we used nucleotide/nucleotide correlation network and community detection methods to analyze the simulated trajectories.Finally we also proposed a hypothesis of ‘‘THF-binding induced allosteric switching'' to explain the THF binding and switch regulation.In conclusion,Firstly,we introduced dynamic correlation network,community network and shortest-path algorithm to study the regulatory factors from the structural perspective.Secondly,synergistic modification induced regulation was proposed to explain TRIM24 recognizing the specific histone modification,THF binding induced allosteric is also proposed to insight into the THF regulation of riboswitch.Thirdly,the study of structural and functional relationship of these factors can help us to deep understand the regulation mechanism for regulatory factors.