scholarly journals The Druggable Pocketome of Corynebacterium diphtheriae: A New Approach for in silico Putative Druggable Targets

2018 ◽  
Vol 9 ◽  
Author(s):  
Syed S. Hassan ◽  
Syed B. Jamal ◽  
Leandro G. Radusky ◽  
Sandeep Tiwari ◽  
Asad Ullah ◽  
...  
Keyword(s):  
In Silico ◽  
Corynebacterium Diphtheriae ◽  
New Approach ◽  
Druggable Targets

G Protein-Coupled Receptors as Challenging Druggable Targets: Insights from in silico Studies

ChemInform ◽  
2006 ◽  
Vol 37 (28) ◽  
Author(s):  
Stefano Moro ◽  
Magdalena Bacilieri ◽  
Francesca Deflorian ◽  
Giampiero Spalluto
Keyword(s):  
G Protein ◽  
In Silico ◽  
G Protein Coupled Receptors ◽  
In Silico Studies ◽  
Druggable Targets ◽  
G Protein Coupled

G protein-coupled receptors as challenging druggable targets: insights from in silico studies

2006 ◽  
Vol 30 (3) ◽  
pp. 301 ◽  
Author(s):  
Stefano Moro ◽  
Magdalena Bacilieri ◽  
Francesca Deflorian ◽  
Giampiero Spalluto
Keyword(s):  
G Protein ◽  
In Silico ◽  
G Protein Coupled Receptors ◽  
In Silico Studies ◽  
Druggable Targets ◽  
G Protein Coupled

scholarly journals A new approach for potential drug target discovery through in silico metabolic pathway analysis using Trypanosoma cruzi genome information

2009 ◽  
Vol 104 (8) ◽  
pp. 1100-1110 ◽  
Author(s):  
Marcelo Alves-Ferreira ◽  
Ana Carolina Ramos Guimarães ◽  
Priscila Vanessa da Silva Zabala Capriles ◽  
Laurent E Dardenne ◽  
Wim M Degrave
Keyword(s):  
Pathway Analysis ◽  
Metabolic Pathway ◽  
In Silico ◽  
Drug Target ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Metabolic Pathway Analysis ◽  
Drug Target Discovery ◽  
New Approach ◽  
Genome Information

scholarly journals Structure-based Druggability Assessment of Anti-virulence Targets from Pseudomonas aeruginosa

2019 ◽  
Vol 20 (12) ◽  
pp. 1189-1203 ◽  
Author(s):  
Thamires Q. Froes ◽  
Regina L. Baldini ◽  
Sandor Vajda ◽  
Marcelo S. Castilho
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Drug Development ◽  
In Silico ◽  
Global Economy ◽  
Drug Targets ◽  
Attractive Alternative ◽  
Antibacterial Drug ◽  
Hotspot Analysis ◽  
Combined Use ◽  
Druggable Targets

Antimicrobial Resistance (AMR) represents a serious threat to health and the global economy. However, interest in antibacterial drug development has decreased substantially in recent decades. Meanwhile, anti-virulence drug development has emerged as an attractive alternative to fight AMR. Although several macromolecular targets have been explored for this goal, their druggability is a vital piece of information that has been overlooked. This review explores this subject by showing how structure- based freely available in silico tools, such as PockDrug and FTMap, might be useful for designing novel inhibitors of the pyocyanin biosynthesis pathway and improving the potency/selectivity of compounds that target the Pseudomonas aeruginosa quorum sensing mechanism. The information provided by hotspot analysis, along with binding site features, reveals novel druggable targets (PhzA and PhzS) that remain largely unexplored. However, it also highlights that in silico druggability prediction tools have several limitations that might be overcome in the near future. Meanwhile, anti-virulence drug targets should be assessed by complementary methods, such as the combined use of FTMap/PockDrug, once the consensus druggability classification reduces the risk of wasting resources on undruggable proteins.

scholarly journals An inverse method for mechanical characterization of heterogeneous diseased arteries using intravascular imaging

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bharath Narayanan ◽  
Max L. Olender ◽  
David Marlevi ◽  
Elazer R. Edelman ◽  
Farhad R. Nezami
Keyword(s):  
In Silico ◽  
Mechanical Characterization ◽  
Imaging Data ◽  
New Approach ◽  
Parameter Recovery ◽  
Material Parameters ◽  
Linear Elastic ◽  
Novel Method

AbstractThe increasing prevalence of finite element (FE) simulations in the study of atherosclerosis has spawned numerous inverse FE methods for the mechanical characterization of diseased tissue in vivo. Current approaches are however limited to either homogenized or simplified material representations. This paper presents a novel method to account for tissue heterogeneity and material nonlinearity in the recovery of constitutive behavior using imaging data acquired at differing intravascular pressures by incorporating interfaces between various intra-plaque tissue types into the objective function definition. Method verification was performed in silico by recovering assigned material parameters from a pair of vessel geometries: one derived from coronary optical coherence tomography (OCT); one generated from in silico-based simulation. In repeated tests, the method consistently recovered 4 linear elastic (0.1 ± 0.1% error) and 8 nonlinear hyperelastic (3.3 ± 3.0% error) material parameters. Method robustness was also highlighted in noise sensitivity analysis, where linear elastic parameters were recovered with average errors of 1.3 ± 1.6% and 8.3 ± 10.5%, at 5% and 20% noise, respectively. Reproducibility was substantiated through the recovery of 9 material parameters in two more models, with mean errors of 3.0 ± 4.7%. The results highlight the potential of this new approach, enabling high-fidelity material parameter recovery for use in complex cardiovascular computational studies.

scholarly journals The use of Bayesian methodology in the development and validation of a tiered assessment approach towards prediction of rat acute oral toxicity

2022 ◽  
Author(s):  
James W. Firman ◽  
Mark T. D. Cronin ◽  
Philip H. Rowe ◽  
Elizaveta Semenova ◽  
John E. Doe
Keyword(s):  
In Silico ◽  
Oral Toxicity ◽  
New Approach ◽  
Combining Data ◽  
Assessment Approach ◽  
In Vivo Testing ◽  
Degree Of Confidence ◽  
Development And Validation

AbstractThere exists consensus that the traditional means by which safety of chemicals is assessed—namely through reliance upon apical outcomes obtained following in vivo testing—is increasingly unfit for purpose. Whilst efforts in development of suitable alternatives continue, few have achieved levels of robustness required for regulatory acceptance. An array of “new approach methodologies” (NAM) for determining toxic effect, spanning in vitro and in silico spheres, have by now emerged. It has been suggested, intuitively, that combining data obtained from across these sources might serve to enhance overall confidence in derived judgment. This concept may be formalised in the “tiered assessment” approach, whereby evidence gathered through a sequential NAM testing strategy is exploited so to infer the properties of a compound of interest. Our intention has been to provide an illustration of how such a scheme might be developed and applied within a practical setting—adopting for this purpose the endpoint of rat acute oral lethality. Bayesian statistical inference is drawn upon to enable quantification of degree of confidence that a substance might ultimately belong to one of five LD50-associated toxicity categories. Informing this is evidence acquired both from existing in silico and in vitro resources, alongside a purposely-constructed random forest model and structural alert set. Results indicate that the combination of in silico methodologies provides moderately conservative estimations of hazard, conducive for application in safety assessment, and for which levels of certainty are defined. Accordingly, scope for potential extension of approach to further toxicological endpoints is demonstrated.

scholarly journals Avaliação de primers universais bacteriano em PCR in silico

2018 ◽  
Vol 9 (2) ◽  
pp. 98
Author(s):  
Matheus Silva Alves ◽  
Luiz Alfredo Torres Sales ◽  
João Victor Nogueira Nojosa ◽  
Roberval Nascimento Moraes Neto ◽  
Alexsander Rodrigues Carvalho Junior ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Mycobacterium Tuberculosis ◽  
Streptococcus Pneumoniae ◽  
Klebsiella Pneumoniae ◽  
In Silico ◽  
Corynebacterium Diphtheriae

As técnicas de biologia molecular são indispensáveis em diversas áreas de pesquisa, dentre elas está a identificação de espécies bacterianas como Staphylococcus aureus, Streptococcus pneumoniae, Pseudomona auruginosa, Klebsiella pneumoniae, Corynebacterium diphtheriae, Mycobacterium tuberculosis e Escherichia coli e para isso utilizam primers universais. Este trabalho busca avaliar a qualidade deste primers universais em amplificar e diferenciar as bactérias descritas. Para isso foi utilizado uma PCR in silico e observados os resultados das amplificações. As amplificações demonstraram uma redundância ou mesmo ineficiência de vários dos primers testados. Palavras-chave: Primers; Bacterias; PCR in silico.

A new approach to determination of bactericidal activity of benzylpenycylin on Corynebacterium diphtheriae

2018 ◽  
Vol 22 (2) ◽  
pp. 368-371
Author(s):  
O.I. Motyka ◽  
O.M. Slesarchuk ◽  
R.B. Pavlii ◽  
K.E. Kapustiak
Keyword(s):  
Antibiotic Therapy ◽  
Bactericidal Activity ◽  
Minimum Bactericidal Concentration ◽  
Corynebacterium Diphtheriae ◽  
Dilution Method ◽  
Bactericidal Action ◽  
New Approach ◽  
The Relationship ◽  
Broth Dilution

Information on the bactericidal activity of benzylpenycylin is important when planning antibiotic therapy for a number of diseases caused by Corynebacterium diphtheriae (endocarditis, bacteremia, septicemia, etc.). However, methods for determining the minimum bactericidal concentration (MBC) of antibiotics are complicated. The aim of the study was to develop a method for testing of diphtheria causative agent susceptibility to the bactericidal action of penicillin without MBC determination. The minimum inhibitory concentrations (MICs) and MBCs in 80 strains of C. diphtheriae were determined using the standard broth dilution method (macromethod). The MICs were registered after 24 and 48 years of growth. After the first day of growth the MIC of penicillin was in the range of 0.017 to 0.5 mg / L, after second day — in the range of 0.035 to 0.5 mg / liter. The increase of the MICs for the second day of growth was observed in 47.5±5.6% of strains. MIC50 and MIC90 both after 24 hours and after 48 hours of growth were 0.13 and 0.25 mg/L, respectively. MBCs of penicillin was in the range of 0.5 to 32.0 mg/L, MBC50 was 4.0 mg/l, MBC90 – 8.0 mg/l. In 35,0±5,3% of the studied strains, high MBCs (8.0 mg / l or higher) was detected. It has been established that in C.diphtheriae the relationship between the MIC and the MBC of penicillin is clearly expressed, taking into account the two values of the MIC – for the first and second day of growth. Investigated strains are divided into three conditional groups: 1) with MIC 0.13 mg/L and basically with low MBCs; 2) with MIC 0.25 mg/L, in most cases are not susceptible to bactericidal action, and 3) strains with MIC 0.5 mg/L and high MBCs. The most pronounced were differences in the prevalence of corynebacteria with high MBCs in two groups of strains: MICs which did not exceed 0.13 mg/L after 24 and 48 hours, and those in whom the MIC was 0.25 mg/L or higher already on the first day of incubation (Student's coefficient t=4.13, p<0.001). The obtained results can be used to improve the methods for determining of corynebacteria susceptibility to antimicrobials.

scholarly journals An integrative in-silico approach for therapeutic target identification in the human pathogen Corynebacterium diphtheriae

PLoS ONE ◽  
2017 ◽  
Vol 12 (10) ◽  
pp. e0186401 ◽  
Author(s):  
Syed Babar Jamal ◽  
Syed Shah Hassan ◽  
Sandeep Tiwari ◽  
Marcus V. Viana ◽  
Leandro de Jesus Benevides ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
In Silico ◽  
Target Identification ◽  
Corynebacterium Diphtheriae ◽  
Human Pathogen
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