scholarly journals Genomic Analyses Identify Novel Molecular Signatures Specific for the Caenorhabditis and other Nematode Taxa Providing Novel Means for Genetic and Biochemical Studies

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 739
Author(s):  
Bijendra Khadka ◽  
Tonuka Chatterjee ◽  
Bhagwati P. Gupta ◽  
Radhey S. Gupta
Keyword(s):  
Nematode Species ◽  
Evolutionary Relationships ◽  
Molecular Characteristics ◽  
Molecular Signatures ◽  
Protein Ligand Interactions ◽  
Conserved Signature Indels ◽  
Biochemical Studies ◽  
Ligand Interactions ◽  
Caenorhabditis Species ◽  
Taxonomic Groups

The phylum Nematoda encompasses numerous free-living as well as parasitic members, including the widely used animal model Caenorhabditis elegans, with significant impact on human health, agriculture, and environment. In view of the importance of nematodes, it is of much interest to identify novel molecular characteristics that are distinctive features of this phylum, or specific taxonomic groups/clades within it, thereby providing innovative means for diagnostics as well as genetic and biochemical studies. Using genome sequences for 52 available nematodes, a robust phylogenetic tree was constructed based on concatenated sequences of 17 conserved proteins. The branching of species in this tree provides important insights into the evolutionary relationships among the studied nematode species. In parallel, detailed comparative analyses on protein sequences from nematodes (Caenorhabditis) species reported here have identified 52 novel molecular signatures (or synapomorphies) consisting of conserved signature indels (CSIs) in different proteins, which are uniquely shared by the homologs from either all genome-sequenced Caenorhabditis species or a number of higher taxonomic clades of nematodes encompassing this genus. Of these molecular signatures, 39 CSIs in proteins involved in diverse functions are uniquely present in all Caenorhabditis species providing reliable means for distinguishing this group of nematodes in molecular terms. The remainder of the CSIs are specific for a number of higher clades of nematodes and offer important insights into the evolutionary relationships among these species. The structural locations of some of the nematodes-specific CSIs were also mapped in the structural models of the corresponding proteins. All of the studied CSIs are localized within the surface-exposed loops of the proteins suggesting that they may potentially be involved in mediating novel protein–protein or protein–ligand interactions, which are specific for these groups of nematodes. The identified CSIs, due to their exclusivity for the indicated groups, provide reliable means for the identification of species within these nematodes groups in molecular terms. Further, due to the predicted roles of these CSIs in cellular functions, they provide important tools for genetic and biochemical studies in Caenorhabditis and other nematodes.

19F-NMR in Target-based Drug Discovery

2019 ◽  
Vol 26 (26) ◽  
pp. 4964-4983 ◽  
Author(s):  
CongBao Kang
Keyword(s):  
Drug Discovery ◽  
Conformational Changes ◽  
Protein Structures ◽  
19F Nmr ◽  
Binding Affinities ◽  
Protein Ligand Interactions ◽  
Compound Libraries ◽  
Ligand Interactions ◽  
Reference Ligand ◽  
Hit Identification

Solution NMR spectroscopy plays important roles in understanding protein structures, dynamics and protein-protein/ligand interactions. In a target-based drug discovery project, NMR can serve an important function in hit identification and lead optimization. Fluorine is a valuable probe for evaluating protein conformational changes and protein-ligand interactions. Accumulated studies demonstrate that 19F-NMR can play important roles in fragment- based drug discovery (FBDD) and probing protein-ligand interactions. This review summarizes the application of 19F-NMR in understanding protein-ligand interactions and drug discovery. Several examples are included to show the roles of 19F-NMR in confirming identified hits/leads in the drug discovery process. In addition to identifying hits from fluorinecontaining compound libraries, 19F-NMR will play an important role in drug discovery by providing a fast and robust way in novel hit identification. This technique can be used for ranking compounds with different binding affinities and is particularly useful for screening competitive compounds when a reference ligand is available.

Combiphore (Structure and Ligand Based Pharmacophore) - Approach for the Design of GPR40 Modulators in the Management of Diabetes

2020 ◽  
Vol 17 (2) ◽  
pp. 233-247
Author(s):  
Krishna A. Gajjar ◽  
Anuradha K. Gajjar
Keyword(s):  
Molecular Docking ◽  
Structural Information ◽  
Docking Studies ◽  
Structural Motif ◽  
Roc Curve Analysis ◽  
Ligand Complex ◽  
Discovery Studio ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Pharmacophore Models

Background: Pharmacophore mapping and molecular docking can be synergistically integrated to improve the drug design and discovery process. A rational strategy, combiphore approach, derived from the combined study of Structure and Ligand based pharmacophore has been described to identify novel GPR40 modulators. Methods: DISCOtech module from Discovery studio was used for the generation of the Structure and Ligand based pharmacophore models which gave hydrophobic aromatic, ring aromatic and negative ionizable as essential pharmacophoric features. The generated models were validated by screening active and inactive datasets, GH scoring and ROC curve analysis. The best model was exposed as a 3D query to screen the hits from databases like GLASS (GPCR-Ligand Association), GPCR SARfari and Mini-Maybridge. Various filters were applied to retrieve the hit molecules having good drug-like properties. A known protein structure of hGPR40 (pdb: 4PHU) having TAK-875 as ligand complex was used to perform the molecular docking studies; using SYBYL-X 1.2 software. Results and Conclusion: Clustering both the models gave RMSD of 0.89. Therefore, the present approach explored the maximum features by combining both ligand and structure based pharmacophore models. A common structural motif as identified in combiphore for GPR40 modulation consists of the para-substituted phenyl propionic acid scaffold. Therefore, the combiphore approach, whereby maximum structural information (from both ligand and biological protein) is explored, gives maximum insights into the plausible protein-ligand interactions and provides potential lead candidates as exemplified in this study.

Xanthine Oxidase and Transforming Growth Factor Beta-activated Kinase 1: potential Targets for Gout Intervention

2020 ◽  
Vol 16 ◽  
Author(s):  
Rajesh Basnet ◽  
Sandhya Khadka ◽  
Buddha Bahadur Basnet ◽  
Til Bahadur Basnet ◽  
Buddhi Bal Chidi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Xanthine Oxidase ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Developed Countries ◽  
Structure Based Drug Design ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Moderate Condition ◽  
Growth Factor Beta

Background: Gout, an inflammatory arthritis, caused by the deposition of monosodium urate crystals into affected joints and other tissues has become one of the major health problems of today's world. The main risk factor for gout is hyperuricemia, which may be caused by excessive or insufficient excretion of uric acid. The incidence is usually in the age group of 30- 50 years, commonly in males. In developed countries, the incidence of gout ranges from 1 to 4%. Despite effective treatments, there has been an increase in the number of cases over the past few decades. Objective: In recent years, the development of targeted drugs in gout has made significant achievements. The global impact of gout continues to increase, and as a result, the focus of disease-modifying therapies remains elusive. In addition, the characterization of available instrumental compounds is urgently needed to explore the use of novel selective and key protein-ligand interactions for the effective treatment of gout. Xanthine oxidase (XO) is a key target in gout to consider the use of XO inhibitors in patients with mild to moderate condition, however, the costs are high and no other direct progress has been made. Despite many XO inhibitors, a selective potent inhibitor for XO is limited. Likewise, in recent years, attention has been focused on different strategies for the discovery and development of new selectivity ligands against transforming growth factor beta-activated kinase 1 (TAK1), a potential therapeutic target for gout. Therefore the insight on human XO structure and TAK1 provides a clue into protein-ligand interactions and provides the basis for molecular modeling and structure-based drug design. Conclusion: In this review, we briefly introduce the clinical characteristics, the development of crystal, inhibitors, and crystal structure of XO and TAK1 protein.

scholarly journals Annelid Diversity: Historical Overview and Future Perspectives

Diversity ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 129
Author(s):  
María Capa ◽  
Pat Hutchings
Keyword(s):  
State Of The Art ◽  
Molecular Taxonomy ◽  
Evolutionary Relationships ◽  
Diverse Group ◽  
Future Perspectives ◽  
Special Issue ◽  
Species Numbers ◽  
Species Complexes ◽  
Taxonomic Groups ◽  
A New Species

Annelida is a ubiquitous, common and diverse group of organisms, found in terrestrial, fresh waters and marine environments. Despite the large efforts put into resolving the evolutionary relationships of these and other Lophotrochozoa, and the delineation of the basal nodes within the group, these are still unanswered. Annelida holds an enormous diversity of forms and biological strategies alongside a large number of species, following Arthropoda, Mollusca, Vertebrata and perhaps Platyhelminthes, among the species most rich in phyla within Metazoa. The number of currently accepted annelid species changes rapidly when taxonomic groups are revised due to synonymies and descriptions of a new species. The group is also experiencing a recent increase in species numbers as a consequence of the use of molecular taxonomy methods, which allows the delineation of the entities within species complexes. This review aims at succinctly reviewing the state-of-the-art of annelid diversity and summarizing the main systematic revisions carried out in the group. Moreover, it should be considered as the introduction to the papers that form this Special Issue on Systematics and Biodiversity of Annelids.

scholarly journals ASFP (Artificial Intelligence based Scoring Function Platform): a web server for the development of customized scoring functions

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Xujun Zhang ◽  
Chao Shen ◽  
Xueying Guo ◽  
Zhe Wang ◽  
Gaoqi Weng ◽  
...  
Keyword(s):  
High Efficiency ◽  
Low Cost ◽  
Pearson Correlation ◽  
Scoring Function ◽  
Web Server ◽  
Scoring Functions ◽  
Protein Ligand Interactions ◽  
Prediction Module ◽  
Ligand Interactions ◽  
Benchmark Datasets

AbstractVirtual screening (VS) based on molecular docking has emerged as one of the mainstream technologies of drug discovery due to its low cost and high efficiency. However, the scoring functions (SFs) implemented in most docking programs are not always accurate enough and how to improve their prediction accuracy is still a big challenge. Here, we propose an integrated platform called ASFP, a web server for the development of customized SFs for structure-based VS. There are three main modules in ASFP: (1) the descriptor generation module that can generate up to 3437 descriptors for the modelling of protein–ligand interactions; (2) the AI-based SF construction module that can establish target-specific SFs based on the pre-generated descriptors through three machine learning (ML) techniques; (3) the online prediction module that provides some well-constructed target-specific SFs for VS and an additional generic SF for binding affinity prediction. Our methodology has been validated on several benchmark datasets. The target-specific SFs can achieve an average ROC AUC of 0.973 towards 32 targets and the generic SF can achieve the Pearson correlation coefficient of 0.81 on the PDBbind version 2016 core set. To sum up, the ASFP server is a powerful tool for structure-based VS.

Redescription and synonymization of Oscheius citri Tabassum, Shahina, Nasira and Erum, 2016 (Rhabditida, Rhabditidae) from India and its taxonomical consequences

2021 ◽  
Vol 95 ◽  
Author(s):  
A. Rana ◽  
A.H. Bhat ◽  
A.K. Chaubey ◽  
V. Půža ◽  
J. Abolafia
Keyword(s):  
Indian Population ◽  
Uttar Pradesh ◽  
Nematode Species ◽  
Molecular Data ◽  
Molecular Characteristics ◽  
Morphometric Characteristics ◽  
High Similarity ◽  
Rdna Sequences ◽  
Indian Strain ◽  
28S Rdna Sequences

Abstract A population of a nematode species belonging to the genus Oscheius was isolated in western Uttar Pradesh, India. Morphological and morphometrical studies on this species showed its high similarity with six species described previously from Pakistan (Oscheius citri, O. cobbi, O. cynodonti, O. esculentus, O. punctatus and O. sacchari). The molecular analysis of the ITS1-5.8S-ITS2 rDNA sequences of the Indian population and the six species described from Pakistan showed that all the sequences are almost identical. Thus, based on morphological and molecular characteristics, all of the six above-mentioned Pakistani species and Indian strain do not differ from each other, hence can be considered synonyms. The correct name for this taxon is the first described species O. citri. Additionally, the phylogenetic analysis of the 18S rDNA and the 28S rDNA sequences showed that Oscheius citri is sister to the clade formed by O. chongmingensis and O. rugaoensis from China. The high similarity of morphological and morphometric characteristics of O. citri and other species, O. maqbooli, O. nadarajani, O. niazii, O. shamimi and O. siddiqii, suggest their conspecificity; however, lack of molecular data for these species does not allow this hypothesis to be tested.

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