The realization of protein functional movement is usually accompanied by specific conformational changes,and there exist some key residues that mediate and control the functional motions of proteins in the allosteric ...The realization of protein functional movement is usually accompanied by specific conformational changes,and there exist some key residues that mediate and control the functional motions of proteins in the allosteric process.In the present work,the perturbation-response scanning method developed by our group was combined with the molecular dynamics(MD)simulation to identify the key residues controlling the functional movement of proteins.In our method,a physical quantity that is directly related to protein specific function was introduced,and then based on the MD simulation trajectories,the perturbation-response scanning method was used to identify the key residues for functional motions,in which the residues that highly correlated with the fluctuation of the function-related quantity were identified as the key residues controlling the specific functional motions of the protein.Two protein systems,i.e.,the heat shock protein 70 and glutamine binding protein,were selected as case studies to validate the effectiveness of our method.Our calculated results are in good agreement with the experimental results.The location of the key residues in the two proteins are similar,indicating the similar mechanisms behind the performance of their biological functions.展开更多
RNA is an important biological macromolecule,which plays an irreplaceable role in many life activities.RNA functions are largely determined by its tertiary structure and the intrinsic dynamics encoded in the structure...RNA is an important biological macromolecule,which plays an irreplaceable role in many life activities.RNA functions are largely determined by its tertiary structure and the intrinsic dynamics encoded in the structure.Thus,how to effective extract structure-encoded dynamics is of great significance for understanding RNA functions.Anisotropic network model(ANM)is an efficient method to investigate macromolecular dynamical properties,which has been widely used in protein studies.However,the performance of the conventional ANM in describing RNA flexibility is not as good as that on proteins.In this study,we proposed a new approach,named force-constant-decayed anisotropic network model(fcdANM),to improve the performance in investigating the dynamical properties encoded in RNA structures.In fcd-ANM,nucleotide pairs in RNA structure were connected by springs and the force constant of springs was decayed exponentially based on the separation distance to describe the differences in the inter-nucleotide interaction strength.The performance of fcd-ANM in predicting RNA flexibility was evaluated using a non-redundant structure database composed of 51 RNAs.The results indicate that fcd-ANM significantly outperforms the conventional ANM in reproducing the experimental B-factors of nucleotides in RNA structures,and the Pearson correlation coefficient between the predicted and experimental nucleotide B-factors was distinctly improved by 21.05%compared to the conventional ANM.Fcd-ANM can serve as a more effective method for analysis of RNA dynamical properties.展开更多
文摘The realization of protein functional movement is usually accompanied by specific conformational changes,and there exist some key residues that mediate and control the functional motions of proteins in the allosteric process.In the present work,the perturbation-response scanning method developed by our group was combined with the molecular dynamics(MD)simulation to identify the key residues controlling the functional movement of proteins.In our method,a physical quantity that is directly related to protein specific function was introduced,and then based on the MD simulation trajectories,the perturbation-response scanning method was used to identify the key residues for functional motions,in which the residues that highly correlated with the fluctuation of the function-related quantity were identified as the key residues controlling the specific functional motions of the protein.Two protein systems,i.e.,the heat shock protein 70 and glutamine binding protein,were selected as case studies to validate the effectiveness of our method.Our calculated results are in good agreement with the experimental results.The location of the key residues in the two proteins are similar,indicating the similar mechanisms behind the performance of their biological functions.
文摘RNA is an important biological macromolecule,which plays an irreplaceable role in many life activities.RNA functions are largely determined by its tertiary structure and the intrinsic dynamics encoded in the structure.Thus,how to effective extract structure-encoded dynamics is of great significance for understanding RNA functions.Anisotropic network model(ANM)is an efficient method to investigate macromolecular dynamical properties,which has been widely used in protein studies.However,the performance of the conventional ANM in describing RNA flexibility is not as good as that on proteins.In this study,we proposed a new approach,named force-constant-decayed anisotropic network model(fcdANM),to improve the performance in investigating the dynamical properties encoded in RNA structures.In fcd-ANM,nucleotide pairs in RNA structure were connected by springs and the force constant of springs was decayed exponentially based on the separation distance to describe the differences in the inter-nucleotide interaction strength.The performance of fcd-ANM in predicting RNA flexibility was evaluated using a non-redundant structure database composed of 51 RNAs.The results indicate that fcd-ANM significantly outperforms the conventional ANM in reproducing the experimental B-factors of nucleotides in RNA structures,and the Pearson correlation coefficient between the predicted and experimental nucleotide B-factors was distinctly improved by 21.05%compared to the conventional ANM.Fcd-ANM can serve as a more effective method for analysis of RNA dynamical properties.
