蛋白质是一种具有空间结构的物质。蛋白质结构预测的主要目标是从已有的大规模的蛋白质数据集中提取有效的信息,从而预测自然界中蛋白质的结构。目前蛋白质结构预测实验存在的一个问题是,缺少能够进一步反映出蛋白质空间结构特征的数据...蛋白质是一种具有空间结构的物质。蛋白质结构预测的主要目标是从已有的大规模的蛋白质数据集中提取有效的信息,从而预测自然界中蛋白质的结构。目前蛋白质结构预测实验存在的一个问题是,缺少能够进一步反映出蛋白质空间结构特征的数据集。当前主流的PDB蛋白质数据集虽然是经过实验测得,但没有利用到蛋白质的空间特征,而且存在掺杂核酸数据和部分数据不完整的问题。针对以上问题,从蛋白质的空间结构角度来研究蛋白质的预测。在原始PDB数据集的基础上,提出了河海图结构蛋白质数据集(Hohai Graphic Protein Data Bank,HohaiGPDB)。该数据集以图结构为基础,表达出了蛋白质的空间结构特征。基于传统Transformer网络模型对新的数据集进行了相关的蛋白质结构预测实验,在HohaiGPDB数据集上的预测准确率可以达到59.38%,证明了HohaiGPDB数据集的研究价值。HohaiGPDB数据集可以作为蛋白质相关研究的通用数据集。展开更多
A fundamental goal in cellular signaling is to understand allosteric communication, the process by which sig-nals originating at one site in a protein propagate reliably to affect distant functional sites. The general...A fundamental goal in cellular signaling is to understand allosteric communication, the process by which sig-nals originating at one site in a protein propagate reliably to affect distant functional sites. The general principles of protein structure that underlie this process remain unknown. Statistical coupling analysis （SCA） is a statistical technique that uses evolutionary data of a protein family to measure correlation between distant functional sites and suggests allosteric communication. In proteins, very distant and small interactions between collections of amino acids provide the communication which can be important for signaling process. In this paper, we present the SCA of protein alignment of the esterase family （pfam ID： PF00756） containing the sequence of antigen 85C secreted by Mycobacterium tuberculosis to identify a subset of interacting residues. Clustering analysis of the pairwise correlation highlighted seven important residue positions in the esterase family alignments. These resi-dues were then mapped on the crystal structure of antigen 85C （PDB ID： 1DQZ）. The mapping revealed corre-lation between 3 distant residues （Asp38, Leu123 and Met125） and suggests allosteric communication between them. This information can be used for a new drug against this fatal disease.展开更多
Using a statistical analysis on beta-sheet structures from the Protein Data Bank, characteristic angles within beta-strands were correlated to the nature of the side chains. The twists were computed from the atomic co...Using a statistical analysis on beta-sheet structures from the Protein Data Bank, characteristic angles within beta-strands were correlated to the nature of the side chains. The twists were computed from the atomic coordinates of five consecutive amino acids’ alpha carbons from single beta-strand sequences. Conditions on the angles for twists to be mainly left-handed are given together with the frequency of occurrence for these non-standard geometrical properties within protein beta-strands. Applications in protein structure prediction and CASP challenges in particular are envisioned by making use of the probabilities of occurrence in protein structures of angle value ranges for given amino acids.展开更多
The accumulation of amyloid β peptide<sub>1-42</sub> (Aβ<sub>1-42</sub>) masses in the brains of Alzheimer’s Disease (AD) patients is associated with neuronal loss and memory deficits. We ha...The accumulation of amyloid β peptide<sub>1-42</sub> (Aβ<sub>1-42</sub>) masses in the brains of Alzheimer’s Disease (AD) patients is associated with neuronal loss and memory deficits. We have previously reported that oral administration of docosahexaenoic acid (DHA, C22:6, n-3) significantly decreases Aβ burden in the brains of AD model rats and that direct in vitro incubation of DHA with Aβ<sub>1-42</sub> curbs the progression of amyloid fibrillation. In the present in silico study, we investigated whether DHA computationally binds with amyloid peptides. The NMR solution structures of Aβ<sub>1-42</sub> were downloaded from the Protein Data Bank (PDB IDs: 1Z0Q and 2BEG). The binding of DHA to Aβ peptides was assessed by molecular docking using both a flexible and rigid docking system. Thioflavin T (ThT) was used as positive control. The chemical structures of ThT and DHA were modeled and converted to the PDB format using PRODRUG. Drug-like properties of DHA were evaluated by ADME (Absorption, Distribution, Metabolism, and Excretion). DHA was found to successfully dock with Aβ<sub>1-42</sub>. Computational analyses of the binding of DHA to Aβ<sub>1-42</sub>, as evaluated by docking studies, further corroborated the inhibitory effect of DHA on in vitro Aβ<sub>1-42</sub> fibrillogenesis and might explain the in vivo reduction of amyloid burden observed in the brains of DHA-administered AD model rats demonstrated in our previous study. These computational data suggest the potential utility of DHA as a preventive medication in Aβ-induced neurodegenerative diseases, including AD.展开更多
文摘蛋白质是一种具有空间结构的物质。蛋白质结构预测的主要目标是从已有的大规模的蛋白质数据集中提取有效的信息,从而预测自然界中蛋白质的结构。目前蛋白质结构预测实验存在的一个问题是,缺少能够进一步反映出蛋白质空间结构特征的数据集。当前主流的PDB蛋白质数据集虽然是经过实验测得,但没有利用到蛋白质的空间特征,而且存在掺杂核酸数据和部分数据不完整的问题。针对以上问题,从蛋白质的空间结构角度来研究蛋白质的预测。在原始PDB数据集的基础上,提出了河海图结构蛋白质数据集(Hohai Graphic Protein Data Bank,HohaiGPDB)。该数据集以图结构为基础,表达出了蛋白质的空间结构特征。基于传统Transformer网络模型对新的数据集进行了相关的蛋白质结构预测实验,在HohaiGPDB数据集上的预测准确率可以达到59.38%,证明了HohaiGPDB数据集的研究价值。HohaiGPDB数据集可以作为蛋白质相关研究的通用数据集。
文摘A fundamental goal in cellular signaling is to understand allosteric communication, the process by which sig-nals originating at one site in a protein propagate reliably to affect distant functional sites. The general principles of protein structure that underlie this process remain unknown. Statistical coupling analysis （SCA） is a statistical technique that uses evolutionary data of a protein family to measure correlation between distant functional sites and suggests allosteric communication. In proteins, very distant and small interactions between collections of amino acids provide the communication which can be important for signaling process. In this paper, we present the SCA of protein alignment of the esterase family （pfam ID： PF00756） containing the sequence of antigen 85C secreted by Mycobacterium tuberculosis to identify a subset of interacting residues. Clustering analysis of the pairwise correlation highlighted seven important residue positions in the esterase family alignments. These resi-dues were then mapped on the crystal structure of antigen 85C （PDB ID： 1DQZ）. The mapping revealed corre-lation between 3 distant residues （Asp38, Leu123 and Met125） and suggests allosteric communication between them. This information can be used for a new drug against this fatal disease.
基金supported by the National Key Research and Development Program of China (2021YFA1301504)the National Natural Science Foundation of China (91953101)the Chinese Academy of Sciences Strategic Priority Research Program (XDB37040202)。
文摘Using a statistical analysis on beta-sheet structures from the Protein Data Bank, characteristic angles within beta-strands were correlated to the nature of the side chains. The twists were computed from the atomic coordinates of five consecutive amino acids’ alpha carbons from single beta-strand sequences. Conditions on the angles for twists to be mainly left-handed are given together with the frequency of occurrence for these non-standard geometrical properties within protein beta-strands. Applications in protein structure prediction and CASP challenges in particular are envisioned by making use of the probabilities of occurrence in protein structures of angle value ranges for given amino acids.
文摘The accumulation of amyloid β peptide<sub>1-42</sub> (Aβ<sub>1-42</sub>) masses in the brains of Alzheimer’s Disease (AD) patients is associated with neuronal loss and memory deficits. We have previously reported that oral administration of docosahexaenoic acid (DHA, C22:6, n-3) significantly decreases Aβ burden in the brains of AD model rats and that direct in vitro incubation of DHA with Aβ<sub>1-42</sub> curbs the progression of amyloid fibrillation. In the present in silico study, we investigated whether DHA computationally binds with amyloid peptides. The NMR solution structures of Aβ<sub>1-42</sub> were downloaded from the Protein Data Bank (PDB IDs: 1Z0Q and 2BEG). The binding of DHA to Aβ peptides was assessed by molecular docking using both a flexible and rigid docking system. Thioflavin T (ThT) was used as positive control. The chemical structures of ThT and DHA were modeled and converted to the PDB format using PRODRUG. Drug-like properties of DHA were evaluated by ADME (Absorption, Distribution, Metabolism, and Excretion). DHA was found to successfully dock with Aβ<sub>1-42</sub>. Computational analyses of the binding of DHA to Aβ<sub>1-42</sub>, as evaluated by docking studies, further corroborated the inhibitory effect of DHA on in vitro Aβ<sub>1-42</sub> fibrillogenesis and might explain the in vivo reduction of amyloid burden observed in the brains of DHA-administered AD model rats demonstrated in our previous study. These computational data suggest the potential utility of DHA as a preventive medication in Aβ-induced neurodegenerative diseases, including AD.
