TAR DNA结合蛋白43(transactive response DNA binding protein 43,TDP-43),一种可变剪切因子,可以特异性地结合富含TG序列的DNA,涉及多种神经退行性疾病.分子动力学模拟方法虽然是研究分子间相互作用强有力的工具,但它非常耗时,且难以...TAR DNA结合蛋白43(transactive response DNA binding protein 43,TDP-43),一种可变剪切因子,可以特异性地结合富含TG序列的DNA,涉及多种神经退行性疾病.分子动力学模拟方法虽然是研究分子间相互作用强有力的工具,但它非常耗时,且难以对有大的构象变化的体系进行充分采样来研究其变构行为.本工作使用粗粒化的基于弹性势的高斯网络模型(Gaussian network model,GNM)研究人TDP-43与靶标DNA间相互作用的动力学.进一步地,利用本课题组之前提出的基于GNM的热力学循环方法识别TDP-43与DNA相互作用的关键残基,其微扰引起了大的结合自由能的变化.DNA结合后,TDP-43上富含正电残基的loop1和loop3片段有较大的柔性损失,这反映了它们在识别和结合中的诱导契合作用.另外发现,基于热力学循环的方法不仅识别到一些与DNA特异性相互作用有关的重要残基,而且识别到一些远离结合界面但在结合引起的分子构象变化中发挥重要作用的残基.本研究有助于理解TDP-43与DNA的特异性相互作用,可为药物设计提供重要信息,另外该方法可以很方便地拓展到其他蛋白质-核酸相互作用动力学的研究.展开更多
Cancer poses a major health problem worldwide.There is a trend of increasing incidence and mortality of several types of cancer in China.Although major breakthroughs have been made in cancer treatment,including advanc...Cancer poses a major health problem worldwide.There is a trend of increasing incidence and mortality of several types of cancer in China.Although major breakthroughs have been made in cancer treatment,including advances in surgical procedures,radiotherapy,chemotherapy,targeted therapy,and immunotherapy,the prognosis of cancer patients is still not optimal.It is widely accepted that malnutrition is commonly seen in cancer patients and that nutritional intervention can improve such patients’overall survival status by supplementing deficient nutrients,regulating abnormal metabolism,improving immune function,and modulating tumor growth.Thus,fighting malnutrition can improve patients’quality of life and survival.This review article provides a summary of development of nutritional oncology as an independent clinical discipline,recent advances,and problems and challenges faced by health care professionals in managing malnutrition among cancer patients.We propose several strategies and approaches to establish nutritional intervention programs in hospitals,including education,clinical nutritional diagnosis and treatment,which may meet the nutrition and treatment goals for patients with cancer in China.We hope that with national-wide development and implementation of nutritional intervention programs,more cancer patient in China will benefit from such endeavors,making nutritional oncology the frontier of cancer treatment not only in China,but also in whole world.展开更多
Gaussian network model(GNM)is an efficient method to investigate the structural dynamics of biomolecules.However,the application of GNM on RNAs is not as good as that on proteins,and there is still room to improve the...Gaussian network model(GNM)is an efficient method to investigate the structural dynamics of biomolecules.However,the application of GNM on RNAs is not as good as that on proteins,and there is still room to improve the model.In this study,two novel approaches,named the weighted GNM(wGNM)and the force-constant-decayed GNM(fcdGNM),were proposed to enhance the performance of ENM in investigating the structural dynamics of RNAs.In wGNM,the force constant for each spring is weighted by the number of interacting heavy atom pairs between two nucleotides.In fcdGNM,all the pairwise nucleotides were connected by springs and the force constant decayed exponentially with the separate distance of the nucleotide pairs.The performance of these two proposed models was evaluated by using a non-redundant RNA structure database composed of 51 RNA molecules.The calculation results show that both the proposed models outperform the conventional GNM in reproducing the experimental B-factors of RNA structures.Compared with the conventional GNM,the Pearson correlation coefficient between the predicted and experimental B-factors was improved by 9.85%and 6.76%for wGNM and fcdGNM,respectively.Our studies provide two candidate methods for better revealing the dynamical properties encoded in RNA structures.展开更多
文摘TAR DNA结合蛋白43(transactive response DNA binding protein 43,TDP-43),一种可变剪切因子,可以特异性地结合富含TG序列的DNA,涉及多种神经退行性疾病.分子动力学模拟方法虽然是研究分子间相互作用强有力的工具,但它非常耗时,且难以对有大的构象变化的体系进行充分采样来研究其变构行为.本工作使用粗粒化的基于弹性势的高斯网络模型(Gaussian network model,GNM)研究人TDP-43与靶标DNA间相互作用的动力学.进一步地,利用本课题组之前提出的基于GNM的热力学循环方法识别TDP-43与DNA相互作用的关键残基,其微扰引起了大的结合自由能的变化.DNA结合后,TDP-43上富含正电残基的loop1和loop3片段有较大的柔性损失,这反映了它们在识别和结合中的诱导契合作用.另外发现,基于热力学循环的方法不仅识别到一些与DNA特异性相互作用有关的重要残基,而且识别到一些远离结合界面但在结合引起的分子构象变化中发挥重要作用的残基.本研究有助于理解TDP-43与DNA的特异性相互作用,可为药物设计提供重要信息,另外该方法可以很方便地拓展到其他蛋白质-核酸相互作用动力学的研究.
文摘Cancer poses a major health problem worldwide.There is a trend of increasing incidence and mortality of several types of cancer in China.Although major breakthroughs have been made in cancer treatment,including advances in surgical procedures,radiotherapy,chemotherapy,targeted therapy,and immunotherapy,the prognosis of cancer patients is still not optimal.It is widely accepted that malnutrition is commonly seen in cancer patients and that nutritional intervention can improve such patients’overall survival status by supplementing deficient nutrients,regulating abnormal metabolism,improving immune function,and modulating tumor growth.Thus,fighting malnutrition can improve patients’quality of life and survival.This review article provides a summary of development of nutritional oncology as an independent clinical discipline,recent advances,and problems and challenges faced by health care professionals in managing malnutrition among cancer patients.We propose several strategies and approaches to establish nutritional intervention programs in hospitals,including education,clinical nutritional diagnosis and treatment,which may meet the nutrition and treatment goals for patients with cancer in China.We hope that with national-wide development and implementation of nutritional intervention programs,more cancer patient in China will benefit from such endeavors,making nutritional oncology the frontier of cancer treatment not only in China,but also in whole world.
文摘Gaussian network model(GNM)is an efficient method to investigate the structural dynamics of biomolecules.However,the application of GNM on RNAs is not as good as that on proteins,and there is still room to improve the model.In this study,two novel approaches,named the weighted GNM(wGNM)and the force-constant-decayed GNM(fcdGNM),were proposed to enhance the performance of ENM in investigating the structural dynamics of RNAs.In wGNM,the force constant for each spring is weighted by the number of interacting heavy atom pairs between two nucleotides.In fcdGNM,all the pairwise nucleotides were connected by springs and the force constant decayed exponentially with the separate distance of the nucleotide pairs.The performance of these two proposed models was evaluated by using a non-redundant RNA structure database composed of 51 RNA molecules.The calculation results show that both the proposed models outperform the conventional GNM in reproducing the experimental B-factors of RNA structures.Compared with the conventional GNM,the Pearson correlation coefficient between the predicted and experimental B-factors was improved by 9.85%and 6.76%for wGNM and fcdGNM,respectively.Our studies provide two candidate methods for better revealing the dynamical properties encoded in RNA structures.
