scholarly journals In silico Structural and Functional Annotation of Tomato Chocolate spot Virus

2021 ◽  
pp. 26-35
Author(s):  
Ftepti B. Jelani
Keyword(s):  
In Silico ◽  
Functional Annotation ◽  
Homology Modelling ◽  
3D Structure ◽  
Strand Break ◽  
Accession Number ◽  
Spot Virus ◽  
Dna Double Strand Break ◽  
Chocolate Spot

Aims: The study aims to predict in-silico the structural and functional annotation of Tomato Chocolate Spot Virus (TCSV) retrieved from Uniprotkb with the accession number C7EXM3. Study design:  To use the In-silico approach for the structural and functional annotation of the Tomato Chocolate Spot Virus. Place and Duration of Study: The research was conducted at the Bioinformatics Unit, Chevron Biotechnology Centre, Modibbo Adama University Yola, Nigeria. Between August 2021 to September 2021. Methodology: The sequence of the Tomato Chocolate Spot Virus was retrieved from Uniprotkb with accession number C7EXM3, Physicochemical characteristics were computed using the ProtParam tool. The sever SOPMA was used for secondary structure analysis (Helix, Sheets and Coils). The tool CELLO v2.5 was used to predict the subcellular localization of the protein. Four different Homology Modelling tools (trRosetta, Lomet, RaptorX and IntFOLD5) were used to predict the 3D structure of the protein, the quality of the predicted proteins was assessed used PROCHECK. Three tools (InterProScan, NCBI conserved domains and Phobius) were used to get the possible function(s) of the protein. Results: ProtParam tool computed various Physical and Chemical properties such as Molecular weight (MW) 20396.96 Daltons, isoelectric point (pI) of 6.92. Instability Index 41.94, and Grand Average Hydropathy (GRAVY) -0.503. SOPMA was used for calculating the secondary structure parameters of the protein as Helices (Hh) 43.48%, Extended strands (Ee) 18.48%, Random coils (Cc) 38.04%. CELLO v2.5 was used for subcellular localization of the protein, it predicted that the protein can be both Nuclear and Cytoplasmic with the reliability of 1.653 and 1.504 respectively. Different Homology modelling tools were used to obtain the best 3D structure of the protein. Furthermore, PROCHECK was used to assess the quality of the models obtained. Model from trRosetta was found to be the best because of the quality of the Ramachandran Plot obtained from PROCHECK which has more than 90% of amino acid in the most favourable regions. NCBI-CDD and interproScan predicted that protein is a DNA double-strand break repair Rad50 ATPase, which is involved in the early steps of DNA double-strand break (DSB) repair. Furthermore, the Phobius server predicted the protein to be non-cytoplasmic in its domain, which means they help target proteins to their final destinations. Conclusion: The study has helped in obtaining the 3D structure of the protein Tomato Chocolate Spot Virus from different Modelling tools, as well as the possible function of the protein.

scholarly journals Homology Modelling and Molecular Docking Studies of Selected Substituted Benzo[d]imidazol-1-yl)methyl)benzimidamide Scaffolds on Plasmodium falciparum Adenylosuccinate Lyase Receptor

2019 ◽  
Vol 13 ◽  
pp. 117793221986553 ◽  
Author(s):  
Gbolahan O Oduselu ◽  
Olayinka O Ajani ◽  
Yvonne U Ajamma ◽  
Benedikt Brors ◽  
Ezekiel Adebiyi
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Docking ◽  
In Silico ◽  
Homology Modelling ◽  
3D Structure ◽  
Docking Studies ◽  
Binding Energies ◽  
Benzimidazole Derivatives ◽  
Adenylosuccinate Lyase ◽  
In Silico Admet

Plasmodium falciparum adenylosuccinate lyase ( PfADSL) is an important enzyme in purine metabolism. Although several benzimidazole derivatives have been commercially developed into drugs, the template design as inhibitor against PfADSL has not been fully explored. This study aims to model the 3-dimensional (3D) structure of PfADSL, design and predict in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) of 8 substituted benzo[ d]imidazol-1-yl)methyl)benzimidamide compounds as well as predict the potential interaction modes and binding affinities of the designed ligands with the modelled PfADSL. PfADSL 3D structure was modelled using SWISS-MODEL, whereas the compounds were designed using ChemDraw Professional. ADMET predictions were done using OSIRIS Property Explorer and Swiss ADME, whereas molecular docking was done with AutoDock Tools. All designed compounds exhibited good in silico ADMET properties, hence can be considered safe for drug development. Binding energies ranged from −6.85 to −8.75 kcal/mol. Thus, they could be further synthesised and developed into active commercial antimalarial drugs.

scholarly journals RIF1 Links Replication Timing with Fork Reactivation and DNA Double-Strand Break Repair

2021 ◽  
Vol 22 (21) ◽  
pp. 11440
Author(s):  
Janusz Blasiak ◽  
Joanna Szczepańska ◽  
Anna Sobczuk ◽  
Michal Fila ◽  
Elzbieta Pawlowska
Keyword(s):  
Therapeutic Potential ◽  
3D Structure ◽  
Replication Timing ◽  
Strand Break ◽  
End Joining ◽  
Long Distance ◽  
Dna Double Strand Break ◽  
Microscopic Studies ◽  
Non Homologous End Joining ◽  
Cycle Regulation

Replication timing (RT) is a cellular program to coordinate initiation of DNA replication in all origins within the genome. RIF1 (replication timing regulatory factor 1) is a master regulator of RT in human cells. This role of RIF1 is associated with binding G4-quadruplexes and changes in 3D chromatin that may suppress origin activation over a long distance. Many effects of RIF1 in fork reactivation and DNA double-strand (DSB) repair (DSBR) are underlined by its interaction with TP53BP1 (tumor protein p53 binding protein). In G1, RIF1 acts antagonistically to BRCA1 (BRCA1 DNA repair associated), suppressing end resection and homologous recombination repair (HRR) and promoting non-homologous end joining (NHEJ), contributing to DSBR pathway choice. RIF1 is an important element of intra-S-checkpoints to recover damaged replication fork with the involvement of HRR. High-resolution microscopic studies show that RIF1 cooperates with TP53BP1 to preserve 3D structure and epigenetic markers of genomic loci disrupted by DSBs. Apart from TP53BP1, RIF1 interact with many other proteins, including proteins involved in DNA damage response, cell cycle regulation, and chromatin remodeling. As impaired RT, DSBR and fork reactivation are associated with genomic instability, a hallmark of malignant transformation, RIF1 has a diagnostic, prognostic, and therapeutic potential in cancer. Further studies may reveal other aspects of common regulation of RT, DSBR, and fork reactivation by RIF1.

Freely Accessible Chemical Database Resources of Compounds for In Silico Drug Discovery

2020 ◽  
Vol 26 (42) ◽  
pp. 7581-7597 ◽  
Author(s):  
JingFang Yang ◽  
Di Wang ◽  
Chenyang Jia ◽  
Mengyao Wang ◽  
GeFei Hao ◽  
...  
Keyword(s):  
Drug Discovery ◽  
In Silico ◽  
3D Structure ◽  
Chemical Information ◽  
Chemical Databases ◽  
Chemical Libraries ◽  
Chemical Database ◽  
Experimental Pressure ◽  
Early Drug

Background: In silico drug discovery has been proved to be a solidly established key component in early drug discovery. However, this task is hampered by the limitation of quantity and quality of compound databases for screening. In order to overcome these obstacles, freely accessible database resources of compounds have bloomed in recent years. Nevertheless, how to choose appropriate tools to treat these freely accessible databases is crucial. To the best of our knowledge, this is the first systematic review on this issue. Objective: The existed advantages and drawbacks of chemical databases were analyzed and summarized based on the collected six categories of freely accessible chemical databases from literature in this review. Results: Suggestions on how and in which conditions the usage of these databases could be reasonable were provided. Tools and procedures for building 3D structure chemical libraries were also introduced. Conclusion: In this review, we described the freely accessible chemical database resources for in silico drug discovery. In particular, the chemical information for building chemical database appears as attractive resources for drug design to alleviate experimental pressure.

scholarly journals In-silico characterization and structure-based functional annotation of a hypothetical protein from Campylobacter jejuni involved in propionate catabolism

2021 ◽  
Vol 19 (4) ◽  
pp. e43
Author(s):  
Lincon Mazumder ◽  
Mehedi Hasan ◽  
Ahmed Abu Rus'd ◽  
Mohammad Ariful Islam
Keyword(s):  
Campylobacter Jejuni ◽  
Protein Interactions ◽  
In Silico ◽  
Functional Annotation ◽  
3D Structure ◽  
Alpha Helix ◽  
Hypothetical Protein ◽  
Random Coil ◽  
Protein Protein Interactions ◽  
In Silico Characterization

Campylobacter jejuni is one of the most prevalent organisms associated with foodborne illness across the globe causing campylobacteriosis and gastritis. Many proteins of C. jejuni are still unidentified. The purpose of this study was to determine the structure and function of a non-annotated hypothetical protein (HP) from C. jejuni. A number of properties like physiochemical characteristics, 3D structure, and functional annotation of the HP (accession No. CAG2129885.1) were predicted using various bioinformatics tools followed by further validation and quality assessment. Moreover, the protein-protein interactions and active site were obtained from the STRING and CASTp server, respectively. The hypothesized protein possesses various characteristics including an acidic pH, thermal stability, water solubility, and cytoplasmic distribution. While alpha-helix and random coil structures are the most prominent structural components of this protein, most of it is formed of helices and coils. Along with expected quality, the 3D model has been found to be novel. This study has identified the potential role of the HP in 2-methylcitric acid cycle and propionate catabolism. Furthermore, protein-protein interactions revealed several significant functional partners. The in-silico characterization of this protein will assist to understand its molecular mechanism of action better. The methodology of this study would also serve as the basis for additional research into proteomic and genomic data for functional potential identification.

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