scholarly journals The Drosophila DCP2 is evolutionarily conserved in sequence and structure : insights from in silico studies of DmDCP2 orthologs and paralogs

2021 ◽  
Author(s):  
Rohit Kunar ◽  
Jagat Kumar Roy
Keyword(s):  
Phylogenetic Tree ◽  
In Silico ◽  
Evolutionary Relationship ◽  
Structural Features ◽  
Quantitative Approach ◽  
Its Sequence ◽  
Multiple Sequence ◽  
Mrna Decapping ◽  
In Silico Studies ◽  
Evolutionarily Conserved

The mRNA decapping proteins (DCPs) function to hydrolyze the 7-methylguanosine cap at the 5 ′ end of mRNAs thereby, exposing the transcript for degradation by the exonuclease(s) and hence, play a pioneering role in the mRNA decay pathway. In Drosophila melanogaster, the mRNA decapping protein 2 (DCP2) is the only catalytically active mRNA decapping enzyme present. Despite its presence being reported across diverse species in the phylogenetic tree, a quantitative approach to the index of its conservation in terms of its sequence has not been reported so far. With structural and mechanistic insights being explored in the yeasts, the insect DCP2 has never been explored in the perspectives of structure and the indices of the conservation of its sequence and/or structure vis-a-vis topological facets. Being an evolutionarily conserved protein, the present endeavor aimed at deciphering the evolutionary relationship(s) and the pattern of conservation of the sequence of DCP2 across the phylogenetic tree as well as in sibling species of D. melanogaster through a semi-quantitative approach relying on multiple sequence alignment and analyses of percentage identity matrices. Since NUDIX proteins are functionally diverse, an attempt to identify the other NUDIX proteins (or, DCP2 paralogs) in D. melanogaster and compare and align their structural features with that of DCP2 through in silico approaches was endeavored in parallel. Our observations provide quantitative and structural bases for the observed evolutionary conservation of DCP2 across the diverse phyla and also, identify and reinforce the structural conservation of the NUDIX family in D. melanogaster.

Amino Acids Sequence-based Analysis of Arginine Deiminase from Different Prokaryotic Organisms: An In Silico Approach

2020 ◽  
Vol 14 (3) ◽  
pp. 235-246
Author(s):  
Sara Abdollahi ◽  
Mohammad H. Morowvat ◽  
Amir Savardashtaki ◽  
Cambyz Irajie ◽  
Sohrab Najafipour ◽  
...  
Keyword(s):  
Amino Acid ◽  
Physicochemical Properties ◽  
Sequence Alignment ◽  
Multiple Sequence Alignment ◽  
In Silico ◽  
Bacterial Species ◽  
Arginine Deiminase ◽  
Antitumor Effects ◽  
Multiple Sequence ◽  
In Silico Studies

Background: Arginine deiminase is a bacterial enzyme, which degrades L-arginine. Some human cancers such as hepatocellular carcinoma (HCC) and melanoma are auxotrophic for arginine. Therefore, PEGylated arginine deiminase (ADI-PEG20) is a good anticancer candidate with antitumor effects. It causes local depletion of L-arginine and growth inhibition in arginineauxotrophic tumor cells. The FDA and EMA have granted orphan status to this drug. Some recently published patents have dealt with this enzyme or its PEGylated form. Objective: Due to increasing attention to it, we aimed to evaluate and compare 30 arginine deiminase proteins from different bacterial species through in silico analysis. Methods: The exploited analyses included the investigation of physicochemical properties, multiple sequence alignment (MSA), motif, superfamily, phylogenetic and 3D comparative analyses of arginine deiminase proteins thorough various bioinformatics tools. Results: The most abundant amino acid in the arginine deiminase proteins is leucine (10.13%) while the least amino acid ratio is cysteine (0.98%). Multiple sequence alignment showed 47 conserved patterns between 30 arginine deiminase amino acid sequences. The results of sequence homology among 30 different groups of arginine deiminase enzymes revealed that all the studied sequences located in amidinotransferase superfamily. Based on the phylogenetic analysis, two major clusters were identified. Considering the results of various in silico studies; we selected the five best candidates for further investigations. The 3D structures of the best five arginine deiminase proteins were generated by the I-TASSER server and PyMOL. The RAMPAGE analysis revealed that 81.4%-91.4%, of the selected sequences, were located in the favored region of arginine deiminase proteins. Conclusion: The results of this study shed light on the basic physicochemical properties of thirty major arginine deiminase sequences. The obtained data could be employed for further in vivo and clinical studies and also for developing the related therapeutic enzymes.

scholarly journals Cloning, Sequencing, and In Silico Analysis of β-Propeller Phytase Bacillus licheniformis Strain PB-13

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Vinod Kumar ◽  
Gopal Singh ◽  
Punesh Sangwan ◽  
A. K. Verma ◽  
Sanjeev Agrawal
Keyword(s):  
Phylogenetic Tree ◽  
Bacillus Licheniformis ◽  
In Silico ◽  
Catalytic Mechanism ◽  
Specific Activity ◽  
In Silico Analysis ◽  
Homology Search ◽  
Multiple Sequence ◽  
Bioinformatic Tools ◽  
C Terminus

β-Propeller phytases (BPPhy) are widely distributed in nature and play a major role in phytate-phosphorus cycling. In the present study, a BPPhy gene from Bacillus licheniformis strain was expressed in E. coli with a phytase activity of 1.15 U/mL and specific activity of 0.92 U/mg proteins. The expressed enzyme represented a full length ORF “PhyPB13” of 381 amino acid residues and differs by 3 residues from the closest similar existing BPPhy sequences. The PhyPB13 sequence was characterized in silico using various bioinformatic tools to better understand structural, functional, and evolutionary aspects of BPPhy class by multiple sequence alignment and homology search, phylogenetic tree construction, variation in biochemical features, and distribution of motifs and superfamilies. In all sequences, conserved sites were observed toward their N-terminus and C-terminus. Cysteine was not present in the sequence. Overall, three major clusters were observed in phylogenetic tree with variation in biophysical characteristics. A total of 10 motifs were reported with motif “1” observed in all 44 protein sequences and might be used for diversity and expression analysis of BPPhy enzymes. This study revealed important sequence features of BPPhy and pave a way for determining catalytic mechanism and selection of phytase with desirable characteristics.

scholarly journals A Comparative Genomic and Phylogenetic Analysis of the Origin and Evolution of the CCN Gene Family

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Kuan Hu ◽  
Yiming Tao ◽  
Juanni Li ◽  
Zhuang Liu ◽  
Xinyan Zhu ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Gene Family ◽  
Evolutionary Relationship ◽  
Evolutionary Process ◽  
Structural Features ◽  
Comparative Genomic ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Origin And Evolution ◽  
Functional Sites

CCN gene family members have recently been identified as multifunctional regulators involved in diverse biological functions, especially in vascular and skeletal development. In the present study, a comparative genomic and phylogenetic analysis was performed to show the similarities and differences in structure and function of CCNs from different organisms and to reveal their potential evolutionary relationship. First, CCN homologs of metazoans from different species were identified. Then we made multiple sequence alignments, MEME analysis, and functional sites prediction, which show the highly conserved structural features among CCN metazoans. The phylogenetic tree was further established, and thus CCNs were found undergoing extensive lineage-specific duplication events and lineage-specific expansion during the evolutionary process. Besides, comparative analysis about the genomic organization and chromosomal CCN gene surrounding indicated a clear orthologous relationship among these species counterparts. At last, based on these research results above, a potential evolutionary scenario was generated to overview the origin and evolution of the CCN gene family.

scholarly journals Potential of Marine Terpenoids against SARS-CoV-2: An In Silico Drug Development Approach

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1505
Author(s):  
Alaka Sahoo ◽  
Shivkanya Fuloria ◽  
Shasank S. Swain ◽  
Sujogya K. Panda ◽  
Mahendran Sekar ◽  
...  
Keyword(s):  
Phylogenetic Tree ◽  
In Silico ◽  
Drug Repurposing ◽  
Pharmacokinetic Profile ◽  
Genomic Diversity ◽  
Ligand Docking ◽  
Multiple Sequence ◽  
Bioactive Natural Products ◽  
Lead Candidate ◽  
Development Approach

In an emergency, drug repurposing is the best alternative option against newly emerged severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, several bioactive natural products have shown potential against SARS-CoV-2 in recent studies. The present study selected sixty-eight broad-spectrum antiviral marine terpenoids and performed molecular docking against two novel SARS-CoV-2 enzymes (main protease or Mpro or 3CLpro) and RNA-dependent RNA polymerase (RdRp). In addition, the present study analysed the physiochemical-toxicity-pharmacokinetic profile, structural activity relationship, and phylogenetic tree with various computational tools to select the ‘lead’ candidate. The genomic diversity study with multiple sequence analyses and phylogenetic tree confirmed that the newly emerged SARS-CoV-2 strain was up to 96% structurally similar to existing CoV-strains. Furthermore, the anti-SARS-CoV-2 potency based on a protein−ligand docking score (kcal/mol) exposed that the marine terpenoid brevione F (−8.4) and stachyflin (−8.4) exhibited similar activity with the reference antiviral drugs lopinavir (−8.4) and darunavir (−7.5) against the target SARS−CoV−Mpro. Similarly, marine terpenoids such as xiamycin (−9.3), thyrsiferol (−9.2), liouvilloside B (−8.9), liouvilloside A (−8.8), and stachyflin (−8.7) exhibited comparatively higher docking scores than the referral drug remdesivir (−7.4), and favipiravir (−5.7) against the target SARS-CoV-2−RdRp. The above in silico investigations concluded that stachyflin is the most ‘lead’ candidate with the most potential against SARS-CoV-2. Previously, stachyflin also exhibited potential activity against HSV-1 and CoV-A59 within IC50, 0.16–0.82 µM. Therefore, some additional pharmacological studies are needed to develop ‘stachyflin’ as a drug against SARS-CoV-2.

scholarly journals MUTATIONAL CONSERVATION, EVOLUTIONARY AND FUNCTIONAL UNDERSTANDING OF PROTO-ONCOGENE c-FOS

2021 ◽  
Vol 9 (4) ◽  
pp. 464-471
Author(s):  
Ruchi Yadav ◽  
Keyword(s):  
Phylogenetic Tree ◽  
Protein Sequence ◽  
Evolutionary Relationship ◽  
Evolutionary Analysis ◽  
Multiple Sequence ◽  
Protein Protein Interaction ◽  
Fos Protein ◽  
Screening And Identification ◽  
Functional Features ◽  
Potential Ligand

c-Fos protein has a function in different types of cancers and is expressed mostly in neurons. It is a human homolog of the viral oncogene. c-Fos is a member of the FOS gene family, these genes interact with the JUN family member to form transcription factors and play a major role in neurons cell development. These genes were also used as an early marker, in neuronal cells to determine early growth and functional features of the neuroendocrine system. Losses in gene function due to mutation leads to neuronal death and have a function in apoptosis. This study has performed mutational conservation in the c-Fos gene across different species. the c-Fos protein sequence was retrieved from the UniProt database (P01100). Total forty nine (49) homologous sequences with the c-Fos protein sequence were identified using the BLASTp tool. Multiple sequence alignment (MSA) and phylogenetic tree construction was done using the MEGA tool. The phylogenetic tree shows that the c-Fos protein of Homosapiens was closely related to Pan troglodytes. UPGMA tree also shows the evolutionary relationship between c-Fos proteins and with the other 49 species included in the dataset. Evolutionary study shows that Myotis species was the common evolutionary species and predicted as root for all other species hence c-Fos gene might have an evolutionary link with these species. Myotis are the most wide diverged species and belongs to the genus of bats. This study highlights the similarity and evolutionary relationship of the c-Fos gene. In this research detailed analysis of evolutionary analysis, PPI, GO, Disease Enrichment was done to understand the functional and evolutionary aspects of c-FOS protein. This study identifies the evolutionary relationship, protein-protein interaction and pathway enrichment of the c-FOS protein. This research can be further extended to include ligand screening and identification of potential ligand against c-FOS protein for drug development and discovery.

scholarly journals Design and In silico Studies of 2,5-Disubstituted 1,2,4-Triazole and 1,3,4-Thiadiazole Derivatives as Pteridine Reductase 1 Inhibitors

2021 ◽  
pp. 166-178
Author(s):  
Shraddha Phadke ◽  
Devender Pathak ◽  
Rakesh Somani
Keyword(s):  
In Silico ◽  
Therapeutic Potential ◽  
Structural Features ◽  
Lipinski’S Rule ◽  
Drug Mechanism ◽  
In Silico Studies ◽  
Lipinski’S Rule Of Five ◽  
Thiadiazole Derivatives

Aims: Design and in silico studies of 2,5-disubstituted triazole and thiadiazole derivatives as Pteridine Reductase 1 inhibitors. With a view to develop effective agents against Leishmaniasis, 2-substituted-5-[(1H-benzimidazol-2yl) methyl] azole derivatives (A1-A12) were designed against the target enzyme Pteridine reductase 1. Methodology: The series was designed by targeting Pteridine reductase 1 which is an enzyme responsible for folate and pterin metabolism. Based on thorough study of the enzyme structure and structural features of ligands required for optimum interaction with the enzyme, a series of 12 compounds consisting of 2,5-disubstituted 1,2,4-triazole and 1,3,4-thiadiazole derivatives was designed. In silico studies were carried out which included docking studies (using V Life software) to understand binding of the compounds with enzyme PTR1, ADMET studies, drug likeness studies for physicochemical properties and bioactivity studies to understand the possible mechanism of action of the compounds. These studies were undertaken using online softwares, molinspiration and admetSAR web servers. Results: Compounds A10 and A12 gave the best docking scores of -59.9765 and -60.4373 respectively that were close to dihydrobiopterin (original substrate). All the compounds complied with Lipinski’s rule of five. Most of the compounds displayed favorable ADMET properties. Conclusion: The 2,5-disubstituted 1,2,4-triazole and 1,3,4-thiadiazole derivatives exhibited good binding affinity for PTR1 enzyme (PDB code: 1E92). The docking scores indicated that enzyme binding may be governed by the nature and size of the substituents on the azole ring. The compounds display well-defined drug-like and pharmacokinetic properties based on Lipinski’s rule of five with additional physicochemical and ADMET parameters. Bioactivity studies suggested the possible drug mechanism as enzyme inhibition. Hence, this study provides evidence for consideration of valuable ligands in 2,5-disubstituted 1,2,4-triazole and 1,3,4-thiadiazole derivatives as potential pteridine reductase 1 inhibitor and further in vitro and in vivo investigations may prove its therapeutic potential.

LemK_MSA: A Multiple Sequence Alignment Method with Sequence Vectorization Based on Lempel-Ziv

2013 ◽  
Vol 284-287 ◽  
pp. 3203-3207 ◽  
Author(s):  
Guo Li Ji ◽  
Jing Ci Yao ◽  
Zi Jiang Yang ◽  
Cong Ting Ye
Keyword(s):  
Sequence Alignment ◽  
High Throughput ◽  
Multiple Sequence Alignment ◽  
Clustering Analysis ◽  
Large Scale ◽  
Evolutionary Relationship ◽  
Structural Features ◽  
Multiple Sequence ◽  
Guide Tree ◽  
Mouse Antibody

In this paper, we propose a method for multiple sequence alignment, LemK_MSA, which integrates Lempel-Ziv based sequence vectorization and k-means clustering analysis. LemK_MSA converts multiple sequence alignment into corresponding 10-dimensional vector alignment by 10 types of copy modes. Then it uses k-means algorithm and NJ algorithm to divide the sequences into several groups and calculate guide tree of each part with the vectors of the sequences. A complete guide tree for multiple sequence alignment could be constructed by merging guide tree of every group. Thus, the time efficiency of processing multiple sequence alignment, especially for large-scale sequences, can be improved. The high-throughput mouse antibody sequences are used to validate the proposed method. Compared to ClustalW, MAFFT and Mbed, LemK_MSA is more than ten times efficient while ensuring the alignment accuracy at the same time. LemK_MSA also provides an effective method to analyze the evolutionary relationship and structural features among high-throughput sequences.

scholarly journals Discovery of New Hits as Antitrypanosomal Agents by In Silico and In Vitro Assays Using Neolignan-Inspired Natural Products from Nectandra leucantha

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4116
Author(s):  
Sheila C. Araujo ◽  
Fernanda S. Sousa ◽  
Thais A. Costa-Silva ◽  
Andre G. Tempone ◽  
João Henrique G. Lago ◽  
...  
Keyword(s):  
In Silico ◽  
Biological Response ◽  
Structural Features ◽  
New Drugs ◽  
In Vitro Assays ◽  
Computational Techniques ◽  
Phytochemical Study ◽  
Ic50 Value ◽  
In Silico Studies

In the present study, the phytochemical study of the n-hexane extract from flowers of Nectandra leucantha (Lauraceae) afforded six known neolignans (1–6) as well as one new metabolite (7), which were characterized by analysis of NMR, IR, UV, and ESI-HRMS data. The new compound 7 exhibited potent activity against the clinically relevant intracellular forms of T. cruzi (amastigotes), with an IC50 value of 4.3 μM and no observed mammalian cytotoxicity in fibroblasts (CC50 > 200 μM). Based on the results obtained and our previous antitrypanosomal data of 50 natural and semi-synthetic related neolignans, 2D and 3D molecular modeling techniques were employed to help the design of new neolignan-based compounds with higher activity. The results obtained from the models were important to understand the main structural features related to the biological response of the neolignans and to aid in the design of new neolignan-based compounds with better biological activity. Therefore, the results acquired from phytochemical, biological, and in silico studies showed that the integration of experimental and computational techniques consists of a powerful tool for the discovery of new prototypes for development of new drugs to treat CD.

Sequencing Analysis and Phylogenetic Tree of HPV Isolated from Breast Cancer Patients at Thi-Qar Province/Iraq

2020 ◽  
pp. 37-40
Keyword(s):  
Nucleotide Sequence ◽  
Phylogenetic Tree ◽  
Evolutionary Relationship ◽  
Nucleotide Sequencing ◽  
Sequencing Analysis ◽  
Breast Cancer Patients ◽  
The North ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
History Of

Genetic variety examination has demonstrated fundamental to the understanding of the epidemiological and developmental history of Papillomavirus (HPV), for the development of accurate diagnostic tests and for efficient vaccine design. The HPV nucleotide diversity has been investigated widely among high-risk HPV types. To make the nucleotide sequence of HPV and do the virus database in Thi-Qar province, and compare sequences of our isolates with previously described isolates from around the world and then draw its phylogenetic tree, this study done. A total of 6 breast formalin-fixed paraffin-embedded (FFPE) of the female patients were included in the study, divided as 4 FFPE malignant tumor and 2 FFPE of benign tumor. The PCR technique was implemented to detect the presence of HPV in breast tissue, and the real-time PCR used to determinant HPV genotypes, then determined a complete nucleotide sequence of HPV of L1 capsid gene, and draw its phylogenetic tree. The nucleotide sequencing finding detects a number of substitution mutation (SNPs) in (L1) gene, which have not been designated before, were identified once in this study population, and revealed that the HPV16 strains have the evolutionary relationship with the South African race, while, the HPV33 and HPV6 showing the evolutionary association with the North American and East Asian race, respectively.

Comparative Study on Mitogen Activated Protein Kinase of Plasmodium Species by Using in silico Method

2012 ◽  
Vol 9 (1) ◽  
pp. 1
Author(s):  
Mohd Fakharul Zaman Raja Yahya ◽  
Hasidah Mohd Sidek
Keyword(s):  
Amino Acid ◽  
In Silico ◽  
Nuclear Export ◽  
Nuclear Export Signal ◽  
Plasmodium Species ◽  
Mitogen Activated Protein Kinase ◽  
Multiple Sequence ◽  
Wide Range ◽  
Mitogen Activated Protein ◽  
Human Plasmodium

Malaria parasites, Plasmodium can infect a wide range of hosts including humans and rodents. There are two copies of mitogen activated protein kinases (MAPKs) in Plasmodium, namely MAPK1 and MAPK2. The MAPKs have been studied extensively in the human Plasmodium, P. falciparum. However, the MAPKs from other Plasmodium species have not been characterized and it is therefore the premise of presented study to characterize the MAPKs from other Plasmodium species-P. vivax, P. knowlesi, P. berghei, P. chabaudi and P.yoelli using a series of publicly available bioinformatic tools. In silico data indicates that all Plasmodium MAPKs are nuclear-localized and contain both a nuclear localization signal (NLS) and a Leucine-rich nuclear export signal (NES). The activation motifs of TDY and TSH were found to be fully conserved in Plasmodium MAPK1 and MAPK2, respectively. The detailed manual inspection of a multiple sequence alignment (MSA) construct revealed a total of 17 amino acid stack patterns comprising of different amino acids present in MAPKJ and MAPK2 respectively, with respect to rodent and human Plasmodia. It is proposed that these amino acid stack patterns may be useful in explaining the disparity between rodent and human Plasmodium MAPKs. 

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