| Ribonucleic acid(RNA)is an indispensable substance in the living organisms.However,for a long time,it is considered that RNA only serves as a messenger carrying genetic information.Because of its simple composition,which only contains four nucleotides in its sequence,scientists once thought that RNA was only used to transmit genetic information and encode amino acids without any other biological functions.But,with the deepening of research,it is gradually realized that RNA can be folded into a certain three-dimensional structure,which plays an essential role in many important biological processes,such as catalysis,regulation,gene expression,growth and evolution of the life activities.Different three-dimensional structures of RNA have different dynamic characteristics,and the various biological functions of RNA usually achieved through its specific conformational motions.Elastic network model(ENM)is an effective method to investigate the intrinsic dynamics encoded in the structure of biomolecules,which has been successfully used in the analysis of protein conformational motions as well as the relationship.between conformational movement and biological functions.Owing to the differences in the structural properties of RNAs compared with those of proteins,the performance of ENM on RNAs is not as good as that on proteins.How to establish a coarse-grained model suitable for RNA and effectively analyze its kinetic properties based on the three-dimensional structure of RNA,and then reveal its biological function is an important issue that needs to be further studied.In this thesis,based on the three-dimensional structure of RNA,the Gaussian network model(GNM)was constructed,in which each nucleotide was simplified as a node and the inter-nucleotide interactions were represented by springs with harmonic potentials.Then,considering the lose-packed tertiary structure of RNA,the conventional GNM was modified and two improved new models more suitable for RNA were proposed in this study,i.e.,the weighted GNM(wGNM)and the force-constant-decayed GNM(fcd GNM).In wGNM,the force constant for each spring in the model was weighted by the number of interacting heavy atom pairs between two nucleotides to account for the different inter-nucleotide interaction strength.In fcd GNM,the force constant between pairwise residues was decayed exponentially with the separate distance of the nucleotide pairs to describe the differences in the interaction strength between nucleotides.The performance of these two enhanced models were evaluated by using a non-redundant RNA structure database composed of 51 RNA molecules.The calculation results show that both the proposed two models can better reproduce the experimental B-factors of RNA structures.Our studies provide effective method to better analyze the dynamical properties encoded in RNAs,which is of great theoretical significances and practical values for drug development,RNA function modification,and treatment of related diseases. |
