Analysis of protein sequence similarity

A new method for similarity analysis of protein sequences is presented in this paper. On the basis of positions, proportion difference and various physicochemical properties of 20 kinds of amino acid in different protein sequences, representative information was extracted from protein sequence and converted into a numeric vector, thus further similarities of protein sequences were analyzed by studying the similarities between vectors. To facilitate the comparison between protein sequences of different length, every protein sequence is first mapped to a fixed-length vector, of which the vector information is relative position of amino acids. Then percentage of 20 kinds of amino acids in the sequence and 3 physicochemical properties are combined to constitute physicochemical information vector. Finally, a one-dimensiona l feature vector with 80 elements(feat ure vector) representing a protein sequence is synthesized. The shortest distance method was applied for cluster analysis on feature vectors so as to analyze similarities in protein sequences. In the numerical experiment part of the article, similarity analysis was conducted for 9 different species of the mitochondrial NADH dehydrogenase. The result of numerical experiment is consistent with the biological fact, which validates the effectiveness of model to a certain extent.

Protein sequence analysis is an important tool for researchers to study on bio-informatics and molecular biology, such as proteins structure and function prediction, phylogenetic classification and different conservation pattern recognition. It is a significant open issue to quickly efficiently find the similar proteins from a large scale of protein repository. This paper proposes a new method based on Discrete Wavelet Transform (DWT) to measure the similarity of protein sequences, i.e. the ACDWT model, as well as two amino acid encoding methods (HPC and ADCC) according to hydropathy properties and dissociation constants respectively. The model employs only the approximation coefficients of DWT so that the feature vector is short. That brings the proposed model a great running time promotion. According to the phylogenic trees about nine ND5 proteins made from our model and others, the experimental results show that our model is efficient and a little better than the others.

In our previous work, we explored the use of graph-theoretic spectral methods for clustering protein sequences [7]. The nodes of the graph represent a set of proteins to be clustered into families and/or super-families. Edges between nodes are undirected and weighted by the similarities between proteins. We constructed a novel similarity function based on BLAST scores. The similarity values are in turn used to construct a Markov matrix representing transition probabilities between every pair of connected proteins. By analyzing the perturbations to the stationary distribution of the Markov matrix (as in [6,4]), we partition the graph into clusters. In this paper, we compare our method with TribeMCL, which modifies random walks, by reinforcing strong edges and pruning weak ones, such that clusters emerge naturally from the graph [3]. We compare these two methods with respect to their ease of use and the quality of the resulting clusters.

Our previous study, based primarily on PCR-denaturing gradient gel electrophoresis and 16S rRNA gene sequencing, focused on the isolation of four bifidobacterial groups from the digestive tract of three bumblebee species. In that study, we proposed that these isolated groups potentially represented novel species of the family Bifidobacteriaceae. One of the four, Bifidobacterium bombi, has been described recently. Strains representing two of the other groups have been classified as members of the genus Bifidobacterium on the basis of positive results for fructose-6-phosphate phosphoketolase activity and analysis of partial 16S rRNA and heat-shock protein 60 (hsp60) gene sequences. Analysis of 16S rRNA gene sequence similarities revealed that the isolates of the first group were affiliated to Bifidobacterium asteroides YIT 11866(T), B. indicum JCM 1302(T) and B. coryneforme ATCC 25911(T) (96.2, 96.0 and 95.9 % sequence similarity, respectively), together with other bifidobacteria showing lower sequence similarity. Additional representatives of the second group were found to be affiliated to Bifidobacterium minimum YIT 4097(T) and B. coryneforme ATCC 25911(T) (96.0 and 96.3 % sequence similarity) and also to other bifidobacteria with lower sequence similarity. These results indicate that the isolates of the two groups belong to novel species within the genus Bifidobacterium. This observation was further substantiated by the results of partial sequencing of hsp60. On the basis of phylogenetic and phenotypic analyses and analysis of 16S rRNA and partial hsp60 gene sequences, we propose two novel species, Bifidobacterium actinocoloniiforme sp. nov. (type strain LISLUCIII-P2(T) = DSM 22766(T) = CCM 7728(T)) and Bifidobacterium bohemicum sp. nov. (type strain JEMLUCVIII-4(T) = DSM 22767(T) = CCM 7729(T)).

Sequence and expression analysis of histone deacetylases in rice

To learn more about the evolutionary origins of Escherichia coli genes, we surveyed systematically for extended sequence similarities among the 1,264 amino acid sequences encoded by chromosomal genes of E. coli K-12 in SwissProt release 26 by using the FASTA program and imposing the following criteria: (i) alignment of segments at least 100 amino acids long and (ii) at least 20% amino acid identity. Altogether, 624 extended alignments meeting the two criteria were identified, corresponding to 577 protein sequences (45.6% of the 1,264 E. coli protein sequences) that had an extended alignment with at least one other E. coli protein sequence. To exclude alignments of questionable biological significance, we imposed a high threshold on the number of gaps allowed in each of the 624 extended alignments, giving us a subset of 464 proteins. The population of 464 alignments has the following characteristics expressed as median values of the group: 254 amino acids in the alignment, representing 86% of the length of the protein, 33% of the amino acids in the alignment being identical, and 1.1 gaps introduced per 100 amino acids of alignment. Where functions are known, nearly all pairs consist of functionally related proteins. This implies that the sequence similarity we detected has biological meaning and did not arise by chance. That a major fraction of E. coli proteins form extended alignments strongly suggests the predominance of duplication and divergence of ancestral genes in the evolution of E. coli genes. The range of degrees of similarity shows that some genes originated more recently than others. There is no evidence of genome doubling in the past, since map distances between genes of sequence-related proteins show no coherent pattern of favored separations.

Molecular cloning and characterization of two alanine aminotransferase genes in the white-backed planthopper Sogatella furcifera

Conservation rates in non-protein-coding regions of five yeast genomes of the genus Saccharomyces were analyzed using multiple whole-genome alignments. This analysis confirmed previously shown decrease in conservation rates observed immediately upstream of the translation start point and downstream of the stop-codon. Further, there was a sharp conservation peak in the upstream regions likely related to the core promoter (-35 bp to +35 bp around TSS) and a conservation peak downstream of the stop-codon whose function is not yet clear. Regulation of leucine and methionine biosynthesis controlled by the global regulator Gcn4p and pathway-specific regulators was analyzed in detail. A candidate alpha-isopropylmalate carrier, YOR271cp, was identified based on conservation of Leu3p binding sites, analysis of ChIP-chip data, protein localization and sequence similarity.

Percolation of annotation errors through hierarchically structured protein sequence databases

Dicer and Dicer like (DCLs) proteins are essential part of small RNA biogenesis pathway, is a type of RNase III digesting long dsRNA (pre-miRNA) to small RNA segments (miRNA). A total of 20 full length of Dicer like proteins (DCL1, DCL2, DCL3 and DCL4) from different organisms available in NCBI were evaluated by bioinformatics tools to investigate properties, structure of DCLs, domain analysis, multiple sequence alignment and phylogenetics tree construction. All DCLs protein sequences have Ribonuclease III protein family that contains RNaseIII domain including Helicase ATP-binding type-1, Helicase C-terminal, Dicer double-stranded RNA-binding fold, PAZ, Ribonuclease III, Double stranded RNA-binding domain (dsRB). Physicochemical analysis offers data such as pI, EC, Al, GRAVY and instability index about these enzymes. Putative phosphorylation sites were also identified which are found to be conserved in plant species and the results showed that the most abundant phosphorylation site is Serine residues in DCLs proteins. Patterns and profile analysis were performed using Prosite and conserved protein motifs subjected to MEME to obtain the best possible matches. The phylogenetics tree represented three major clusters and similar DCLs protein sequences of different plant species clustered together. The obtained results could be used for further in silico analysis and homology modeling studies. Keywords: Dicer, DCLs, miRNA, RNase, In silico analysis. *Corresponding Author: Ertugrul Filiz (e-mail: ertugrulfiliz@gmail.com). (Received: 25.05.2012 Accepted: 24.01.2013)

Insect chitinases (CHTs) and chitinase‐like proteins, which belong to family 18 glycosylhydrolases (GH‐18), have been detected in molting fluid and gut tissues and are predicted to mediate the digestion of chitin present in the exoskeleton and peritrophic matrix (PM) in the gut to chitooligosaccharides. Based on amino acid sequence similarity and phylogenetic analysis, insect chitinase family proteins have been classified into eight groups (group I to VIII). The chitinases belonging to different groups have distinctly different developmental patterns of expression and tissue specificity, suggestive of distinct biological functions.CHT7s belong to Group III chitinase contain two catalytic domains and one CBD. The catalytic domain 1 of this group of chitinases exhibits greater sequence similarity to one another than to the catalytic domain 2 in the same protein(s), suggesting distinct functions and/or evolutionary origins for each of these two catalytic domains. This group of chitinases, unlike most insect CHTs, possesses a predicted transmembrane segment at the N‐terminal region. The recombinant T. castaneum CHT7 that was expressed in Hi‐5 insect cells was bound to the cell membrane. Apparently, the catalytic domains of this CHT face the extracellular space as revealed by its ability to hydrolyze an artificial chitin substrate added to the medium.DsRNA mediated post‐transcription gene silencing (RNAi) for several chitinases and chitinase‐like genes in Tribolium castaneum and demonstrated that chitinases belong to groups I (TcCHT5), II (TcCHT10) and V (TcIDGF4) play roles of insect molting. In other hand, RNAi for TcCHT7 did not affect any types of molting such as larval‐larval, larval‐pupal and pupal‐adult. The resulting pupae (and adults), however, failed to wing‐expansion and abdominal contraction suggesting that TcCHT7 may function in tissue differentiation rather than in molting.

According to the advancement of experimental techniques in molecular biology, genomic and protein sequence databases are increasing in size exponentially, and mean sequence lengths are also increasing. Because the sizes of these databases become larger, it is difficult to search similar sequences in biological databases with significant homologies to a query sequence. In this paper, we present the N-gram indexing method to retrieve similar sequences fast, precisely and comparably. This method regards a protein sequence as a text written in language of 20 amino acid codes, adapts N-gram tokens of fixed-length as its indexing scheme for sequence strings. After such tokens are indexed for all the sequences in the database, sequences can be searched with information retrieval algorithms. Using this new method, we have developed a protein sequence search system named as ProSeS (PROtein Sequence Search). ProSeS is a protein sequence analysis system which provides overall analysis results such as similar sequences with significant homologies, predicted subcellular locations of the query sequence, and major keywords extracted from annotations of similar sequences. We show experimentally that the N-gram indexing approach saves the retrieval time significantly, and that it is as accurate as current popular search tool BLAST.

The disease caused by the Oropouche virus has been on the rise in countries such as Brazil. Currently, there are no antiviral therapies or vaccines available for treating this viral infection and few studies of Oropouche proteins are available. This study provides an overview of the virus and its associated disease, while also examining the use of computational methodologies to support antiviral drug design. The methods employed include searching for Oropouche virus protein models in databases, analysis of structural sequence similarities, search of molecular cavities and pharmacophore, and evaluation of potential druggability, and comparing cavity similarities with other 3D protein models. The study identified the existence of 3D protein model, the glycoprotein Gc, which is crucial for the microorganism's cell penetration. The search for similar amino acid sequences revealed similarities with several other viruses. The cavity search generated several models deemed druggable. Consequently, a pharmacophore model was created and used to identify similar cavities in other protein models, suggesting thousands of similar cavities. These cavities present ligands that can be further studied for their interactions with the cavities generated by the viral protein. This manuscript highlights Oropouche Fever and the application of in silico methodologies for developing fusion inhibitors of the Oropouche virus in human cells. The study provides a valid roadmap for discovering new potential antiviral agents against the Oropouche virus.

Structural plasticity of naturally occurring proteins allows them to change their shape in response to environmental factors such as pH, temperature, or binding partners. This ability to adopt different conformations is essential for many biological processes. While computational methods have been applied to design and redesign protein sequences that fold to a single ordered and stable state, the computational design of protein sequences with high sequence similarity that adopt well-defined but structurally divergent structures remains an outstanding challenge. Here, we designed 28 pairs of sequences using Monte Carlo simulation, denoted as (a1, b1), (a2, b2), (a3, b3), ..., (a28, b28), where ai and bi represent sequences adopting the 3-α fold and 4β + α fold, respectively. Among these, we identified three sets of fold-switching protein sequences, (a1, b1), (a2, b2), and (a3, b3): one with 89.29% sequence similarity and two others with 87.50% sequence similarity. This reflects the ability of statistical potential to finely balance competing structural constraints. The designed sequences differ by only few residues; however, they possess different tertiary structures: a 3-α helix fold and a 4β + α fold. In addition, sequence variants for a1, a2, and a3 are also designed using rational design guided by sequence analysis, and the results show striking outcomes: single point mutations, specifically D26C or A39F in a1, are sufficient to induce fold switching from the 3-α fold to the 4β + α fold while maintaining 98% sequence similarity with the parent sequence. Together, these findings suggest that the design approach is successful in designing fold-switching sequences that are compatible with their respective target structures. This work also ensures that the developed one-body and two-body statistical potentials are successful in designing protein sequences that exhibit fold conservation and the fold-switching phenomenon, as well as stability at the respective target structures.

Comparative protein analysis of the chitin metabolic pathway in extant organisms: A complex network approach