scholarly journals DrugHybrid_BS: Using Hybrid Feature Combined With Bagging-SVM to Predict Potentially Druggable Proteins

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuxin Gong ◽  
Bo Liao ◽  
Peng Wang ◽  
Quan Zou
Keyword(s):  
Drug Targets ◽  
New Drugs ◽  
Biological Macromolecules ◽  
Potential Drug ◽  
Predictive Tool ◽  
Hybrid Features ◽  
Cross Covariance ◽  
Key Features ◽  
Potential Drug Targets

Drug targets are biological macromolecules or biomolecule structures capable of specifically binding a therapeutic effect with a particular drug or regulating physiological functions. Due to the important value and role of drug targets in recent years, the prediction of potential drug targets has become a research hotspot. The key to the research and development of modern new drugs is first to identify potential drug targets. In this paper, a new predictor, DrugHybrid_BS, is developed based on hybrid features and Bagging-SVM to identify potentially druggable proteins. This method combines the three features of monoDiKGap (k = 2), cross-covariance, and grouped amino acid composition. It removes redundant features and analyses key features through MRMD and MRMD2.0. The cross-validation results show that 96.9944% of the potentially druggable proteins can be accurately identified, and the accuracy of the independent test set has reached 96.5665%. This all means that DrugHybrid_BS has the potential to become a useful predictive tool for druggable proteins. In addition, the hybrid key features can identify 80.0343% of the potentially druggable proteins combined with Bagging-SVM, which indicates the significance of this part of the features for research.

Structure, Function and Interactions of Tau: Particular Focus on Potential Drug Targets for the Treatment of Tauopathies

2018 ◽  
Vol 17 (5) ◽  
pp. 325-337 ◽  
Author(s):  
Hojjat Borna ◽  
Kasim Assadoulahei ◽  
Gholamhossein Riazi ◽  
Asghar Beigi Harchegani ◽  
Alireza Shahriary
Keyword(s):  
Tau Protein ◽  
Drug Targets ◽  
Brain Injuries ◽  
Potential Drug ◽  
Microtubule Network ◽  
Wide Range ◽  
Potential Risk Factors ◽  
Range Of Functions ◽  
Potential Drug Targets

Background & Objective: Neurodegenrative diseases are among the most widespread lifethreatening disorders around the world in elderly ages. The common feature of a group of neurodegenerative disorders, called tauopathies, is an accumulation of microtubule associated protein tau inside the neurons. The exact mechanism underlying tauopathies is not well-understood but several factors such as traumatic brain injuries and genetics are considered as potential risk factors. Although tau protein is well-known for its key role in stabilizing and organization of axonal microtubule network, it bears a broad range of functions including DNA protection and participation in signaling pathways. Moreover, the flexible unfolded structure of tau facilitates modification of tau by a wide range of intracellular enzymes which in turn broadens tau function and interaction spectrum. The distinctive properties of tau protein concomitant with the crucial role of tau interaction partners in the progression of neurodegeneration suggest tau and its binding partners as potential drug targets for the treatment of neurodegenerative diseases. Conclusion: This review aims to give a detailed description of structure, functions and interactions of tau protein in order to provide insight into potential therapeutic targets for treatment of tauopathies.

Abstract 4627: The role of human endogenous retroviral proteins in the development of Merlin-deficient tumors and as potential drug targets

2016 ◽  
Author(s):  
Emmanuel Maze ◽  
Shona Reeves ◽  
David Hilton ◽  
Lucy Provenzano ◽  
Robert Belshaw ◽  
...  
Keyword(s):  
Drug Targets ◽  
Potential Drug ◽  
Potential Drug Targets

scholarly journals Genomewide Analysis of Mode of Action of the S-Adenosylmethionine Analogue Sinefungin in Leishmania infantum

mSystems ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Arijit Bhattacharya ◽  
Mansi Sharma ◽  
Charles Packianathan ◽  
Barry P. Rosen ◽  
Philippe Leprohon ◽  
...  
Keyword(s):  
Drug Targets ◽  
Protozoan Parasite ◽  
Cell Types ◽  
Biosynthetic Pathways ◽  
Potential Drug ◽  
Pathogenic Parasite ◽  
Potential Drug Targets ◽  
Chemotherapeutic Interventions

The two main cellular metabolic one-carbon donors are reduced folates and S-adenosylmethionine, whose biosynthetic pathways have proven highly effective in chemotherapeutic interventions in various cell types. Sinefungin, a nucleoside analogue of S-adenosylmethionine, was shown to have potent activity against the protozoan parasite Leishmania. Here, we studied resistance to sinefungin using whole-genome approaches as a way to further our understanding of the role of S-adenosylmethionine in this parasite and to reveal novel potential drug targets. These approaches allowed the characterization of novel features related to S-adenosylmethionine function in Leishmania which could further help in the development of sinefungin-like compounds against this pathogenic parasite.

scholarly journals Mefloquine interferes with glycolysis in schistosomula of Schistosoma mansoni via inhibition of enolase

Parasitology ◽  
2012 ◽  
Vol 139 (4) ◽  
pp. 497-505 ◽  
Author(s):  
THERESIA MANNECK ◽  
JENNIFER KEISER ◽  
JOACHIM MÜLLER
Keyword(s):  
Mass Spectrometry ◽  
Schistosoma Mansoni ◽  
Sodium Fluoride ◽  
Drug Targets ◽  
Potential Role ◽  
Glycolytic Enzyme ◽  
Potential Drug ◽  
Crude Extracts ◽  
Potential Drug Targets

SUMMARYThe antimalarial drug mefloquine has promising antischistosomal properties killing haematophagous adult schistosomes as well as schistosomula. The mode of action and involved drug targets of mefloquine in Schistosoma mansoni schistosomula are unknown. In order to identify mefloquine-binding proteins and thus potential drug targets, mefloquine affinity chromatography with S. mansoni schistosomula crude extracts was performed. We found one specific mefloquine-binding protein that was identified by mass spectrometry as the glycolytic enzyme enolase (Q27877). Enolase activity assays were performed on schistosomula crude extracts and on the recombinant enolase Q27877 expressed in Escherichia coli. In schistosomula crude extracts enolase activity was inhibited by mefloquine and by the enolase inhibitor sodium fluoride, while activity of the recombinant enolase was not affected. In contrast to enolase from crude extracts, recombinant Q27877 did not bind to mefloquine-agarose. Using isothermal microcalorimetry, we next investigated the metabolic inhibition of mefloquine and 3 known glycolytic inhibitors in Schistosoma spp., namely sodium fluoride, 3-bromopyruvate and menadione on schistosomula in the presence or absence of glucose. We found that in the presence of glucose, schistosomula were less affected by mefloquine, sodium fluoride and 3-bromopyruvate, whereas glucose had no protective effect when schistosomula had been exposed to menadione. These results suggest a potential role of mefloquine as an inhibitor of glycolysis, at least in stages where other targets like haem degradation are not relevant.

scholarly journals New directions for drug discovery in psychiatric disease

2002 ◽  
Vol 4 (4) ◽  
pp. 336-341
Keyword(s):  
Animal Model ◽  
Drug Discovery ◽  
Animal Models ◽  
Drug Targets ◽  
Disease Process ◽  
Psychiatric Disease ◽  
Potential Drug ◽  
New Directions ◽  
Potential Drug Targets

Although many new potential drug targets have been discovered subsequent to the cloning of the human genome and the discovery of most of the relevant receptors, the role of these receptors in psychiatric disease is still not clear. We argue that research into the disease process leading to new animal models that can be transposed to man is critical to drug discovery, and present an example of an animal model for schizophrenia using electroencephalography.

scholarly journals Hunting for cures: Genomics and new diseasecontrol strategies

2003 ◽  
Vol 25 (6) ◽  
pp. 19-21
Author(s):  
Michael Ginger
Keyword(s):  
Drug Discovery ◽  
Drug Targets ◽  
New Drugs ◽  
Potential Drug ◽  
Discovery Process ◽  
Drug Discovery Process ◽  
Genomic Technologies ◽  
Potential Drug Targets

New drugs are needed urgently to win the war against parasites that cause many serious diseases that are endemic or resurgent in some of the World's poorest countries. Post-genomic technologies provide a powerful resource that can be exploited during the drug-discovery process. With genome sequencers able to uncover secrets from even the most experimentally intractable of pathogens, the complete and annotated genomes from a number of the most medically important parasites are now, or will soon be, published. Already, the information that has been released from these projects has been put to good use in identifying new potential drug targets.

scholarly journals Evaluating potential drug targets through human loss-of-function genetic variation

2019 ◽  
Author(s):  
Eric Vallabh Minikel ◽  
Konrad J Karczewski ◽  
Hilary C Martin ◽  
Beryl B Cummings ◽  
Nicola Whiffin ◽  
...  
Keyword(s):  
Drug Targets ◽  
Large Scale ◽  
Human Genetics ◽  
Positional Distribution ◽  
Model Organism ◽  
New Drugs ◽  
Potential Drug ◽  
Loss Of Function ◽  
Potential Drug Targets

AbstractHuman genetics has informed the clinical development of new drugs, and is beginning to influence the selection of new drug targets. Large-scale DNA sequencing studies have created a catalogue of naturally occurring genetic variants predicted to cause loss of function in human genes, which in principle should provide powerfulin vivomodels of human genetic “knockouts” to complement model organism knockout studies and inform drug development. Here, we consider the use of predicted loss-of-function (pLoF) variation catalogued in the Genome Aggregation Database (gnomAD) for the evaluation of genes as potential drug targets. Many drug targets, including the targets of highly successful inhibitors such as aspirin and statins, are under natural selection at least as extreme as known haploinsufficient genes, with pLoF variants almost completely depleted from the population. Thus, metrics of gene essentiality should not be used to eliminate genes from consideration as potential targets. The identification of individual humans harboring “knockouts” (biallelic gene inactivation), followed by individual recall and deep phenotyping, is highly valuable to study gene function. In most genes, pLoF alleles are sufficiently rare that ascertainment will be largely limited to heterozygous individuals in outbred populations. Sampling of diverse bottlenecked populations and consanguineous individuals will aid in identification of total “knockouts”. Careful filtering and curation of pLoF variants in a gene of interest is necessary in order to identify true LoF individuals for follow-up, and the positional distribution or frequency of true LoF variants may reveal important disease biology. Our analysis suggests that the value of pLoF variant data for drug discovery lies in deep curation informed by the nature of the drug and its indication, as well as the biology of the gene, followed by recall-by-genotype studies in targeted populations.

scholarly journals Potassium channels as potential drug targets for limb wound repair and regeneration

2019 ◽  
Vol 3 (1) ◽  
pp. 22-33
Author(s):  
Wengeng Zhang ◽  
Pragnya Das ◽  
Sarah Kelangi ◽  
Marianna Bei
Keyword(s):  
Ion Channels ◽  
Potassium Channels ◽  
Drug Targets ◽  
Wound Repair ◽  
Limb Regeneration ◽  
Large Family ◽  
Potential Drug ◽  
Mouse Limb ◽  
Potential Drug Targets

Abstract Background Ion channels are a large family of transmembrane proteins, accessible by soluble membrane-impermeable molecules, and thus are targets for development of therapeutic drugs. Ion channels are the second most common target for existing drugs, after G protein-coupled receptors, and are expected to make a big impact on precision medicine in many different diseases including wound repair and regeneration. Research has shown that endogenous bioelectric signaling mediated by ion channels is critical in non-mammalian limb regeneration. However, the role of ion channels in regeneration of limbs in mammalian systems is not yet defined. Methods To explore the role of potassium channels in limb wound repair and regeneration, the hindlimbs of mouse embryos were amputated at E12.5 when the wound is expected to regenerate and E15.5 when the wound is not expected to regenerate, and gene expression of potassium channels was studied. Results Most of the potassium channels were downregulated, except for the potassium channel kcnj8 (Kir6.1) which was upregulated in E12.5 embryos after amputation. Conclusion This study provides a new mouse limb regeneration model and demonstrates that potassium channels are potential drug targets for limb wound healing and regeneration.

scholarly journals Identification of Missing Carbon Fixation Enzymes as Potential Drug Targets in Mycobacterium Tuberculosis

2018 ◽  
Vol 15 (3) ◽  
Author(s):  
Amit Katiyar ◽  
Harpreet Singh ◽  
Krishna Kant Azad
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Drug Target ◽  
Drug Targets ◽  
Metabolic Networks ◽  
Carbon Fixation ◽  
New Drugs ◽  
Metabolic Adaptation ◽  
Potential Drug ◽  
Genes Encoding ◽  
Potential Drug Targets

Abstract Metabolic adaptation to the host environment has been recognized as an essential mechanism of pathogenicity and the growth of Mycobacterium tuberculosis (Mtb) in the lungs for decades. The Mtb uses CO2 as a source of carbon during the dormant or non-replicative state. However, there is a lack of biochemical knowledge of its metabolic networks. In this study, we investigated the CO2 fixation pathways (such as ko00710 and ko00720) most likely involved in the energy production and conversion of CO2 in Mtb. Extensive pathway evaluation of 23 completely sequenced strains of Mtb confirmed the existence of a complete list of genes encoding the relevant enzymes of the reductive tricarboxylic acid (rTCA) cycle. This provides the evidence that an rTCA cycle may function to fix CO2 in this bacterium. We also proposed that as CO2 is plentiful in the lungs, inhibition of CO2 fixation pathways (by targeting the relevant CO2 fixation enzymes) could be used in the expansion of new drugs against the dormant Mtb. In support of the suggested hypothesis, the CO2 fixation enzymes were confirmed as a potential drug target by analyzing a number of attributes necessary to be a good bacterial target.

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