The broken-stick model for amino acid composition in proteins

Summary The relative abundances among the amino acids, which are functionally similar to one another, were explained by random partition of a unit interval.     

Dietary deficiencies of single amino acids: Whole-body amino acid composition of adult rats

Abstract

To ascertain whether chronic amino acid deficiency alters the amino acid composition of the body, 44 adult female rats were randomly allocated to one of 11 treatments which included one control group, ingesting an adequate diet with balanced protein, and ten deficient groups in which one group received protein-deficient diets and the other groups consumed diets each deficient in a single essential amino acid. The degree of deficiency was adjusted to achieve a gradual decline in body weight to 85% of the initial weight and was then adjusted so that this weight was maintained until the end of the experiment at 93 days, when the rats were killed. Deficient rats had lower absolute weights of liver, gastrointestinal tract and muscle than animals given the adequate diet but greater relative weights (% of body weight) of heart and kidneys. There were no significant differences amongst groups in percentages of lipid, nitrogen, protein plus lipid or dry matter. Chronic marginal amino acid deficiencies did not selectively alter amino acid composition.     

Predicting the cofactors of oxidoreductases based on amino acid composition distribution and Chou's amphiphilic pseudo-amino acid composition

Predicting the cofactors of oxidoreductases plays an important role in inferring their catalytic mechanism. Feature extraction is a critical part in the prediction systems, requiring raw sequence data to be transformed into appropriate numerical feature vectors while minimizing information loss. In this paper, we present an amino acid composition distribution method for extracting useful features from primary sequence, and the k-nearest neighbor was used as the classifier. The overall prediction accuracy evaluated by the 10-fold cross-validation reached 90.74%. Comparing our method with other eight feature extraction methods, the improvement of the overall prediction accuracy ranged from 3.49% to 15.74%. Our experimental results confirm that the method we proposed is very useful and may be used for other bioinformatical predictions. Interestingly, when features extracted by our method and Chou's amphiphilic pseudo-amino acid composition were combined, the overall accuracy could reach 92.53%.     

Unique amino acid composition of proteins in halophilic bacteria

The amino acid compositions of proteins from halophilic archaea were compared with those from non-halophilic mesophiles and thermophiles, in terms of the protein surface and interior, on a genome-wide scale. As we previously reported for proteins from thermophiles, a biased amino acid composition also exists in halophiles, in which an abundance of acidic residues was found on the protein surface as compared to the interior. This general feature did not seem to depend on the individual protein structures, but was applicable to all proteins encoded within the entire genome. Unique protein surface compositions are common in both halophiles and thermophiles. Statistical tests have shown that significant surface compositional differences exist among halophiles, non-halophiles, and thermophiles, while the interior composition within each of the three types of organisms does not significantly differ. Although thermophilic proteins have an almost equal abundance of both acidic and basic residues, a large excess of acidic residues in halophilic proteins seems to be compensated by fewer basic residues. Aspartic acid, lysine, asparagine, alanine, and threonine significantly contributed to the compositional differences of halophiles from meso- and thermophiles. Among them, however, only aspartic acid deviated largely from the expected amount estimated from the dinucleotide composition of the genomic DNA sequence of the halophile, which has an extremely high G+C content (68%). Thus, the other residues with large deviations (Lys, Ala, etc.) from their non-halophilic frequencies could have arisen merely as "dragging effects" caused by the compositional shift of the DNA, which would have changed to increase principally the fraction of aspartic acid alone.     

Degradation of neurofilament proteins by purified human brain cathepsin D

Abstract: Cathepsin D (CD) was purified to homogeneity from postmortem human cerebral cortex. Incubation of CD with human neurofilament proteins (NFPs) prepared by axonal flotation led to the rapid degradation of the 200,000, 160,000, and 70,000 NFP subunits (200K, 160K, and 70K) which had been separated by one-or two-dimensional sodium dodecyl sulfate-polyacrylámide gel electrophoresis (SDS-PAGE). Degradation was appreciable at enzyme activity-to-substrate protein ratios that were two-to threefold lower than those in unfractionated homogenates from cerebral cortex. Quantitative measurements of NFPs separated by PAGE revealed that, at early stages of digestion, the 160K NFP was somewhat more rapidly degraded than the 70K subunit while the 200K NFP had an intermediate rate of degradation. At sufficiently high enzyme concentrations, all endogenous proteins in human NF preparations were susceptible to the action of CD. Human brain CD also degraded cytoskeletal proteins in NF preparations from mouse brain with a similar specificity. To identify specific NFP breakdown products, antisera against each of the major NFPs were applied to nitrocellulose electroblots of NFPs separated by two-dimensional SDS-PAGE. In addition to detecting the 200K, 160K, and 70K NFP in human NF preparations, the antisera also detected nonoverlapping groups of polypeptides resembling those in NF preparations from fresh rat brain. When human NF preparations were incubated with CD, additional polypeptides were released in specific patterns from each NFP subunit. Some of the immuno-cross-reactive fragments generated from NFPs by CD comigrated on two-dimensional gels with polypeptides present in unincubated preparations. These results demonstrate that NFPs and other cytoskel-etal proteins are substrates for CD. The physiological significance of these findings and the possible usefulness of analyzing protein degradation products for establishing the action of proteinases in vivo are discussed.     

The breakdown of the individual neurofilament proteins by cathepsin D

In a continuing study of proteolysis of CNS proteins by CNS enzymes, neurofilament proteins (210 K, 155 K, 70 K) and desmin were separated, and the breakdown of individual proteins by purified brain cathepsin D was measured and compared to breakdown by plasma thrombin. With both cathepsin D and thrombin, the rate of breakdown of the 70 K protein was the highest, followed by the 155 K, and that of the 210 K was the lowest. With each substrate cathepsin D breakdown was the highest at pH 3; small but significant breakdown could be seen at pH 6. The pattern of intermediate breakdown products depended on pH, with greater amounts of fragments detected at higher pH, and the patterns with the two enzymes were different. We showed that differences exist in cleavage sites and breakdown rates of the neurofilament proteins. The capacity of the cathepsin D present in the tissue to hydrolyze these substrates was high, even at pH close to neutral, and was greatly in excess of that needed for physiological neurofilament turnover.     

Correlations between nucleotide frequencies and amino acid composition in 115 bacterial species

We studied the correlations between amino acid composition and mononucleotide and dinucleotide frequencies in 115 bacterial genomes of varying G+C content. Observed amino acid frequencies were compared with those expected from the actual mononucleotide and dinucleotide frequencies. Both mononucleotide and dinucleotide frequencies correlate well with the amino acid frequency, with dinucleotide frequencies doing so better. Despite the strong correlations, some of the observed amino acid frequencies, in particular for Arg, Val, Asp, Glu, Ser, and Cys, were consistently different from predicted values in all genomes. We suggest that this variation from predicted values is a consequence of selection pressure at the level of amino acids, while the close correspondence to the predictions in residues such as Thr, Phe, Lys, and Asn arises only from mutation and selection pressure at the level of the nucleic acid sequences.     

半滑舌鳎受精卵、卵黄囊仔鱼和开口仔鱼氨基酸及脂肪酸的变化

采用气相色谱仪和氨基酸分析仪测定了半滑舌鳎(Cynoglossus semilaevis)受精卵、卵黄囊仔鱼和开口仔鱼的氨基酸与脂肪酸组成的变化。结果表明:总氨基酸组成在受精卵和卵黄囊仔鱼之间变化明显,但是在卵黄囊仔鱼和开口仔鱼之间只有细微的变化。开口仔鱼与其摄食的轮虫的总必需氨基酸组成相关。受精卵、卵黄囊仔鱼、开口仔鱼的游离氨基酸含量分别为139 mg/g、3.6 mg/g和2.5 mg/g,占总氨基酸含量的22.3%、3.6%和2.5%。饱和脂肪酸的总量从受精卵到卵黄囊仔鱼明显下降,但是发育到开口仔鱼含量无显著变化。单不饱和脂肪酸和多不饱和脂肪酸的总量在不同发育阶段无显著变化,而EPA和DHA的含量从卵黄囊仔鱼到开口仔鱼有明显下降。这表明在早期发育阶段半滑舌鳎主要利用饱和脂肪酸作为能量代谢的基质,对饱和脂肪酸的利用程度大于单不饱和脂肪酸和多不饱和脂肪酸。半滑舌鳎似乎需要长链的多不饱和脂肪酸如EPA、DHA和ARA。     

Processing of neurofilament proteins from perikaryal to axonal type

In previous studies, neuronal cell bodies, excised by hand from bovine spinal ganglia, were analyzed and heterogeneous intermediate and high molecular weight neurofilament proteins that differed in electrophoretic mobility from their axonal counterparts were demonstrated (1, 2). In the present experiment, intermediate and high molecular weight neurofilament proteins of the axonal type were treated with alkaline phosphatase, and neurofilament proteins enriched in perikaryal type proteins were labeled with³²P. Results showed that neurofilament proteins were phosphorylated after their translation, in the perikarya and the proximal portion of the axon, and suggested that phosphorylation was responsible for the differences between axonal and perikaryal neurofilament proteins.Special Issue dedicated to Prof. Holger Hydén.     

Protein location prediction using atomic composition and global features of the amino acid sequence

Subcellular location of protein is constructive information in determining its function, screening for drug candidates, vaccine design, annotation of gene products and in selecting relevant proteins for further studies. Computational prediction of subcellular localization deals with predicting the location of a protein from its amino acid sequence. For a computational localization prediction method to be more accurate, it should exploit all possible relevant biological features that contribute to the subcellular localization. In this work, we extracted the biological features from the full length protein sequence to incorporate more biological information. A new biological feature, distribution of atomic composition is effectively used with, multiple physiochemical properties, amino acid composition, three part amino acid composition, and sequence similarity for predicting the subcellular location of the protein. Support Vector Machines are designed for four modules and prediction is made by a weighted voting system. Our system makes prediction with an accuracy of 100, 82.47, 88.81 for self-consistency test, jackknife test and independent data test respectively. Our results provide evidence that the prediction based on the biological features derived from the full length amino acid sequence gives better accuracy than those derived from N-terminal alone. Considering the features as a distribution within the entire sequence will bring out underlying property distribution to a greater detail to enhance the prediction accuracy.     

Isolation and amino acid sequence of two new PR-4 proteins from wheat

We have purified and characterized two new pathogenesis-related (PR) proteins from wheat belonging to the PR-4 family. We named the proteins wheatwin3 and wheatwin4 in analogy with the previously characterized wheatwin1 and wheatwin2. Their isoelectric points were 7.1 and 8.4, respectively. We determined the complete amino acid sequence of both proteins by a rapid approach based on the knowledge of the primary structures of the homologous wheatwin1 and wheatwin2. Wheatwin3 differs from wheatwin1 in one substitution at position 88, while wheatwin4 differs from wheatwin2 in one substitution at position 78. The secondary structure and solvent accessibility of these residues were determined on the three-dimensional model of wheatwin1. Residue 88 was very accessible and was located in a flexible region. Preliminary results indicate that, like wheatwin1 and wheatwin2, wheatwin3 and wheatwin4 have antifungal activity.     

Differences in amino acids composition and coupling patterns between mesophilic and thermophilic proteins

Summary. Thermophilic proteins show substantially higher intrinsic thermal stability than their mesophilic counterparts. Amino acid composition is believed to alter the intrinsic stability of proteins. Several investigations and mutagenesis experiment have been carried out to understand the amino acid composition for the thermostability of proteins. This review presents some generalized features of amino acid composition found in thermophilic proteins, including an increase in residue hydrophobicity, a decrease in uncharged polar residues, an increase in charged residues, an increase in aromatic residues, certain amino acid coupling patterns and amino acid preferences for thermophilic proteins. The differences of amino acids composition between thermophilic and mesophilic proteins are related to some properties of amino acids. These features provide guidelines for engineering mesophilic protein to thermophilic protein. Authors’ addresses: Yuan-Jiang Pan, Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Zhejiang University Road 38, Hangzhou 310027, China; Wei-Fen Li, Microbiology Division, College of Animal Science, Zhejiang University, Hangzhou 310029, China     

Identification of DNA-binding proteins by incorporating evolutionary information into pseudo amino acid composition via the top-n-gram approach

DNA-binding proteins are crucial for various cellular processes and hence have become an important target for both basic research and drug development. With the avalanche of protein sequences generated in the postgenomic age, it is highly desired to establish an automated method for rapidly and accurately identifying DNA-binding proteins based on their sequence information alone. Owing to the fact that all biological species have developed beginning from a very limited number of ancestral species, it is important to take into account the evolutionary information in developing such a high-throughput tool. In view of this, a new predictor was proposed by incorporating the evolutionary information into the general form of pseudo amino acid composition via the top-n-gram approach. It was observed by comparing the new predictor with the existing methods via both jackknife test and independent data-set test that the new predictor outperformed its counterparts. It is anticipated that the new predictor may become a useful vehicle for identifying DNA-binding proteins. It has not escaped our notice that the novel approach to extract evolutionary information into the formulation of statistical samples can be used to identify many other protein attributes as well.     

Conservation of the basic pattern of cellular amino acid composition of archaeobacteria during biological evolution and the putative amino acid composition of primitive life forms

Summary. Previous studies showed that the cellular amino acid composition obtained by amino acid analysis of whole cells, differs such as eubacteria, protozoa, fungi and mammalian cells. These results suggest that the difference in the cellular amino acid composition reflects biological changes as the result of evolution. However, the basic pattern of cellular amino acid composition was relatively constant in all organisms examined. In the present study, we examined archaeobacteria, because they are considered important in understanding the relationship between biological evolution and cellular amino acid composition. The cellular amino acid compositions of Archaeoglobus fulgidus, Pyrococcus horikoshii, Methanobacterium thermoautotrophicum and Methanococcus jannaschii differed slightly from each other, but were similar to those determined from codon usage data, based on the complete genomes. Thus, the cellular amino acid composition reflects biological evolution. We suggest that primitive forms of life appearing on earth at the end of prebiotic evolution had a similar-cellular amino acid composition. Received November 28, 2000 Accepted January 30, 2001     

iNSP-GCAAP: Identifying nonclassical secreted proteins using global composition of amino acid properties

Nonclassical secreted proteins (NSPs) refer to a group of proteins released into the extracellular environment under the facilitation of different biological transporting pathways apart from the Sec/Tat system. As experimental determination of NSPs is often costly and requires skilled handling techniques, computational approaches are necessary. In this study, we introduce iNSP-GCAAP, a computational prediction framework, to identify NSPs. We propose using global composition of a customized set of amino acid properties to encode sequence data and use the random forest (RF) algorithm for classification. We used the training dataset introduced by Zhang et al. (Bioinformatics, 36(3), 704–712, 2020) to develop our model and test it with the independent test set in the same study. The area under the receiver operating characteristic curve on that test set was 0.9256, which outperformed other state-of-the-art methods using the same datasets. Our framework is also deployed as a user-friendly web-based application to support the research community to predict NSPs.     

利用伪氨基酸组分和支持向量机预测抗冻蛋白

抗冻蛋白是一类具有提高生物抗冻能力的蛋白质。抗冻蛋白能够特异性的与冰晶相结合,进而阻止体液内冰核的形成与生长。因此,对抗冻蛋白的生物信息学研究对生物工程发展。提高作物抗冻性有重要的推动作用。本文采用由400条抗冻蛋白序列和400条非抗冻蛋白序列构成数据集,以伪氨基酸组分为特征,利用支持向量机分类算法预测抗冻蛋白,对训练集预测精度达到91．3％,对测试集预测精度达到78．8％。该结果证明伪氨基酸组分能够很好的反映抗冻蛋白特性,并能够用于预测抗冻蛋白。     

Relationship between G + C in silent sites of codons and amino acid composition of human proteins

Summary We have investigated the relationship between the G + C content of silent (synonymous) sites in codons and the amino acid composition of encoded proteins for approximately 1,600 human genes. There are positive correlations between silent site G + C and the proportions of codons for Arg, Pro, Ala, Trp, His, Gln, and Leu and negative ones for Tyr, Phe, Asn, Ile, Lys, Asp, Thr, and Glu. The median proteins coded by groups of genes that differ in silent-site G + C content also differ in amino acid composition, as do some proteins coded by homologous genes. The pattern of compositional change can be largely explained by directional mutation pressure, the genetic code, and differences in the frequencies of accepted amino acid substitutions; the shifts in protein composition are likely to be selectively neutral.Offprint requests to: D.W. Collins     

Relationship of amino acid composition and molecular weight of antifreeze glycopeptides to non-colligative freezing point depression

Many polar fishes synthesize a group of eight glycopeptides that exhibit a non-colligative lowering of the freezing point of water. These glycopeptides range in molecular weight between 2600 and 33700. The largest glycopeptides [1–5] lower the freezing point more than the small ones on a weight basis and contain only two amino acids, alanine and threonine, with the disaccharide galactose-N-acetyl-galactosamine attached to threonine. The smaller glycopeptides, 6, 7, and 8, also lower the freezing point and contain proline, which periodically substitutes for alanine. Glycopeptides with similar antifreeze properties isolated from the saffron cod and the Atlantic tomcod contain an additional amino acid, arginine, which substitutes for threonine in glycopeptide 6. In this study we address the question of whether differences in amino acid composition or molecular weight between large and small glycopeptides are responsible for the reduced freezing point depressing capability of the low molecular weight glycopeptides. The results indicate that the degree of amino acid substitutions that occur in glycopeptides 6–8 do not have a significant effect on the unusual freezing point lowering and that the observed decrease in freezing point depression with smaller glycopeptides can be accounted for on the basis of molecular weight.     

Evaluation of compositional nonrandomness in proteins

Summary Cornish-Bowden and Marson have recently suggested that the finite sampling component of Q, a measure of nonrandomness in the amino acid composition of proteins, may have been underestimated because it was calculated on the basis of the genetic code table frequencies rather than on the basis of the average natural abundance with which the twenty amino acids actually occur in proteins. This underestimate would lead to an overestimate of Q_c a measure of selective effects above and beyond those imposed by the average natural abundance of the amino acids. In this paper the finite sampling component of Q is quantitatively estimated on the basis of these natural abundances and found to reduce Q_c from its previous average value of 24.3 to the lower value of 9.7, with the standard deviation of the population of Q_c values being 12.5. Individual Q_c values are given for 81 protein families of mean composition per 61 codons of Ala_5.3 Arg_2.4 Asn_3.0 Asp_3.6 Cys_1.5 Gln_2.6 Glu_3.5 Gly_4.7 His_1.3 Ile_3.4 Leu_4.5 Lys_4.2 Met_1.0 Phe_2.3 Pro_2.3 Ser_4.2 Thr_3.6 Trp_0.8 Tyr_2.6 Val_4.2. The mean Q_c value of 9.7 is notably small, and indicates that quantitatively minimal adjustments away from the average protein composition are necessary to maintain many different biological functions. This small value, however, is shown to differ significantly from the value of zero expected were the natural abundances of the amino acids the only selective constraint. These small deviations from the natural abundances are thus effectively selected for in the Darwinian sense.     

胞外多肽信使的氨基酸偏好特征研究及应用

植物细胞外多肽信使已经被证实是植物信号转导中重要的第一信使。通过运用生物信息学的方法,分析比较了已知的植物、动物及微生物的胞外多肽信使的氨基酸序列,发现这些来自不同种的胞外多肽信使具有共同的氨基酸偏好特征。利用在线工具对胞外多肽信使的氨基酸偏好特征进行了验证,并根据细胞外多肽信使的氨基酸偏好特征推测了新的植物胞外多肽信使,这些结果对发现新的植物胞外多肽信使将会有所帮助。