Non-stochastic and stochastic linear indices of the molecular pseudograph’s atom-adjacency matrix: a novel approach for computational in silico screening and “rational” selection of new lead antibacterial agents

2005 ◽  
Vol 12 (3) ◽  
pp. 255-271 ◽  
Author(s):  
Yovani Marrero-Ponce ◽  
Ricardo Medina Marrero ◽  
Francisco Torrens ◽  
Yamile Martinez ◽  
Milagros García Bernal ◽  
...  
Keyword(s):  
Adjacency Matrix ◽  
In Silico ◽  
Antibacterial Agents ◽  
Rational Selection ◽  
In Silico Screening ◽  
Novel Approach ◽  
Selection Of

scholarly journals In silico screening of alleged miRNAs associated with cell competition: an emerging cellular event in cancer

2015 ◽  
Vol 20 (5) ◽  
Author(s):  
Manish Patel ◽  
Bhavesh Antala ◽  
Neeta Shrivastava
Keyword(s):  
In Silico ◽  
Expression Profiles ◽  
Drosophila Genome ◽  
Cell Competition ◽  
In Silico Screening ◽  
Regulation Of Expression ◽  
Expression Of Genes ◽  
Cancer Initiation ◽  
Experimental Approaches ◽  
Selection Of

AbstractCell competition is identified as a crucial phenomenon for cancer and organ development. There is a possibility that microRNAs (miRNAs) may play an important role in the regulation of expression of genes involved in cell competition. In silico screening of miRNAs is an effort to abridge, economize and expedite the experimental approaches to identification of potential miRNAs involved in cell competition, as no study has reported involvement of miRNAs in cell competition to date. In this study, we used multiple screening steps as follows: (i) selection of cell competition related genes of Drosophila through a literature survey; (ii) homology study of selected cell competition related genes; (iii) identification of miRNAs that target conserved cell competitionrelated genes through prediction tools; (iv) sequence conservation analysis of identified miRNAs with human genome; (v) identification of conserved cell competition miRNAs using their expression profiles and exploration of roles of their homologous human miRNAs. This study led to the identification of nine potential cell competition miRNAs in the Drosophila genome. Importantly, eighteen human homologs of these nine potential Drosophila miRNAs are well reported for their involvement in different types of cancers. This confirms their probable involvement in cell competition as well, because cell competition is well justified for its involvement in cancer initiation and maintenance.

Gold-Aptamer-Nanoconstructs Engineered to Detect Conserved Enteroviral Nucleic Acid Sequences

2019 ◽  
Author(s):  
Veeren Chauhan ◽  
Mohamed M Elsutohy ◽  
C Patrick McClure ◽  
Will Irving ◽  
Neil Roddis ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
In Silico ◽  
Point Of Care ◽  
Lateral Flow ◽  
Nucleic Acid Sequence ◽  
In Silico Screening ◽  
Lateral Flow Assays ◽  
Life Threatening ◽  
Software And Hardware ◽  
Nucleic Acid Sequences

<p>Enteroviruses are a ubiquitous mammalian pathogen that can produce mild to life-threatening disease. Bearing this in mind, we have developed a rapid, accurate and economical point-of-care biosensor that can detect a nucleic acid sequences conserved amongst 96% of all known enteroviruses. The biosensor harnesses the physicochemical properties of gold nanoparticles and aptamers to provide colourimetric, spectroscopic and lateral flow-based identification of an exclusive enteroviral RNA sequence (23 bases), which was identified through in silico screening. Aptamers were designed to demonstrate specific complementarity towards the target enteroviral RNA to produce aggregated gold-aptamer nanoconstructs. Conserved target enteroviral nucleic acid sequence (≥ 1x10<sup>-7</sup> M, ≥1.4×10<sup>-14</sup> g/mL), initiates gold-aptamer-nanoconstructs disaggregation and a signal transduction mechanism, producing a colourimetric and spectroscopic blueshift (544 nm (purple) > 524 nm (red)). Furthermore, lateral-flow-assays that utilise gold-aptamer-nanoconstructs were unaffected by contaminating human genomic DNA, demonstrated rapid detection of conserved target enteroviral nucleic acid sequence (< 60 s) and could be interpreted with a bespoke software and hardware electronic interface. We anticipate our methodology will translate in-silico screening of nucleic acid databases to a tangible enteroviral desktop detector, which could be readily translated to related organisms. This will pave-the-way forward in the clinical evaluation of disease and complement existing strategies at overcoming antimicrobial resistance.</p>

Design and in-silico screening of Peptide Nucleic Acid (PNA) inspired novel pronucleotide scaffolds targeting COVID-19

2020 ◽  
Vol 16 ◽  
Author(s):  
Bichismita Sahu ◽  
Santosh Kumar Behera ◽  
Rudradip Das ◽  
Tanay Dalvi ◽  
Arnab Chowdhury ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
In Silico ◽  
Peptide Nucleic Acid ◽  
Large Set ◽  
Nonstructural Proteins ◽  
In Silico Screening ◽  
Replication Process ◽  
Enveloped Virus ◽  
Treatment Regimens ◽  
Novel Coronavirus

Introduction: The outburst of the novel coronavirus COVID-19, at the end of December 2019 has turned itself into a pandemic taking a heavy toll on human lives. The causal agent being SARS-CoV-2, a member of the long-known Coronaviridae family, is a positive sense single-stranded enveloped virus and quite closely related to SARS-CoV. It has become the need of the hour to understand the pathophysiology of this disease, so that drugs, vaccines, treatment regimens and plausible therapeutic agents can be produced. Methods: In this regard, recent studies uncovered the fact that the viral genome of SARS-CoV-2 encodes nonstructural proteins like RNA dependent RNA polymerase (RdRp) which is an important tool for its transcription and replication process. A large number of nucleic acid based anti-viral drugs are being repurposed for treating COVID-19 targeting RdRp. Few of them are in the advanced stage of clinical trials including Remdesivir. While performing close investigation of the large set of nucleic acid based drugs, we were surprised to find that the synthetic nucleic acid backbone is explored very little or rare. Results: We have designed scaffolds derived from peptide nucleic acid (PNA) and subjected them for in-silico screening systematically. These designed molecules have demonstrated excellent binding towards RdRp. Compound 12 was found to possess similar binding affinity as Remdesivir with comparable pharmacokinetics. However, the in-silico toxicity prediction indicates compound 12 may be a superior molecule which can be explored further due to its excellent safety-profile with LD50 (12,000mg/kg) as opposed to Remdesivir (LD50 =1000mg/kg). Conclusion: Compound 12 falls in the safe category of class 6. Synthetic feasibility, equipotent binding and very low toxicity of this peptide nucleic acid derived compounds can serve as a leading scaffold to design, synthesize and evaluate many of similar compounds for the treatment of COVID-19.

In silico screening of pyridoxine carbamates for Anti-Alzheimer’s activities

2020 ◽  
Vol 20 ◽  
Author(s):  
Dnyaneshwar Baswar ◽  
Abha Sharma ◽  
Awanish Mishra
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
In Silico ◽  
Neurodegenerative Disorder ◽  
Biological Activities ◽  
Cholinergic Neurons ◽  
In Silico Screening ◽  
In Silico Studies ◽  
Bbb Permeability ◽  
Ld50 Value

Background: Alzheimer’s disease (AD), an irreversible complex neurodegenerative disorder, is most common type of dementia, with progressive loss of cholinergic neurons. Based on the multi- factorial etiology of Alzheimer’s disease, novel ligands strategy appears as up-coming approach for the development of newer molecules against AD. This study is envisaged to investigate anti-Alzheimer’s potential of 10 synthesized compounds. The screening of compounds (1-10) was carried out using in silico techniques. Methods: For in silico screening of physicochemical properties of compounds molinspiration property engine v.2018.03, Swiss ADME online web-server and pkCSM ADME were used. For pharmacodynamic prediction PASS software while toxicity profile of compounds were analyzed through ProTox-II online software. Simultaneously, molecular docking analysis was performed on mouse AChE enzyme (PDB ID:2JGE, obtained from RSCB PDB) using Auto Dock Tools 1.5.6. Results: Based on in silico studies, compound 9 and 10 have been found to have better drug likeness, LD50 value, and better anti-Alzheimer’s, nootropic activities. However, these compounds had poor blood brain barrier (BBB) permeability. Compound 4 and 9 were predicted with better docking score for AChE enzyme. Conclusion: The outcome of in silico studies have suggested, out of various substitutions at different positions of pyridoxine-carbamate, compound 9 have shown promising drug likeness, with better safety and efficacy profile for anti-Alzheimer’s activity. However, BBB permeability appears as one the major limitation of all these compounds. Further studies are required to confirm its biological activities.

In silico Screening and Molecular Interaction Studies of Tetrahydrocannabinol and its Derivatives with Acetylcholine Binding Protein

2018 ◽  
Vol 12 (2) ◽  
pp. 181-190 ◽  
Author(s):  
Priya P. Panigrahi ◽  
Ramit Singla ◽  
Ankush Bansal ◽  
Moacyr Comar Junior ◽  
Vikas Jaitak ◽  
...  
Keyword(s):  
Molecular Interaction ◽  
In Silico ◽  
Binding Protein ◽  
In Silico Screening ◽  
Acetylcholine Binding Protein ◽  
Interaction Studies

scholarly journals The use of cement concrete pavements for roads, depending on climatic conditions

2019 ◽  
Vol 13 (3) ◽  
pp. 235-240
Author(s):  
Iryna Solonenko
Keyword(s):  
European Union ◽  
Statistical Models ◽  
Road Network ◽  
The European Union ◽  
Rational Selection ◽  
Cement Concrete ◽  
The Road ◽  
Road Pavement ◽  
Operational Characteristics ◽  
Selection Of

The development of road network infrastructure is an important component of the economic development of the European Union. Updating of the road network contributes to the integration of the economies of countries into a coherent whole. The road network provides the free movement of citizens, the movement of goods and the effective implementation of various services. The increase in the length of the road network leads to an increase in the financial and material costs necessary to ensure its maintenance and repair. One of the ways to reduce costs is by strengthening the physic-mechanical and operational characteristics of the pavement due to the widespread use of cement concrete. The quality of the pavement of cement concrete depends largely on the rational selection of its composition. This allows a significant increase in the durability of road pavement. The purpose of the research was: the development of recommendations for the rational selection of the composition of the road pavement material of cement concrete, aimed at upgrading longevity, and taking into account its frost resistance grade. According to the goal, the following tasks were developed: the analyses of the climatic zones in which the road network of the European Union is located; the development of a research plan, a selection of the response function and influence factors; the study of physico-mechanical and operational characteristics of the researched material of road pavement; on the basis of the obtained data, the calculation of the complex of experimental-statistical models, which describe the physico-mechanical and operational characteristics of the road pavement material; on the basis of experimental statistical models, a method was proposed for selecting the rational compositions of the cement concrete pavement road material depending on the conditions of its application. The results presented in the article can be used in engineering and scientific practice for the selection of road pavement from cement concrete for highways.

Development of a Performance-Related Framework for Asphalt Mixture Design for the Illinois Tollway

2021 ◽  
pp. 036119812110148
Author(s):  
Behnam Jahangiri ◽  
Punyaslok Rath ◽  
Hamed Majidifard ◽  
William G. Buttlar
Keyword(s):  
Asphalt Mixture ◽  
Field Performance ◽  
Compact Tension ◽  
T Test ◽  
Novel Approach ◽  
Final Adjustment ◽  
Development And Validation ◽  
High Degree ◽  
Selection Of

Various agencies have begun to research and introduce performance-related specifications (PRS) for the design of modern asphalt paving mixtures. The focus of most recent studies has been directed toward simplified cracking test development and evaluation. In some cases, development and validation of PRS has been performed, building on these new tests, often by comparison of test values to accelerated pavement test studies and/or to limited field data. This study describes the findings of a comprehensive research project conducted at Illinois Tollway, leading to a PRS for the design of mainline and shoulder asphalt mixtures. A novel approach was developed, involving the systematic establishment of specification requirements based on: 1) selection of baseline values based on minimally acceptable field performance thresholds; 2) elevation of thresholds to account for differences between short-term lab aging and expected long-term field aging; 3) further elevation of thresholds to account for variability in lab testing, plus variability in the testing of field cores; and 4) final adjustment and rounding of thresholds based on a consensus process. After a thorough evaluation of different candidate cracking tests in the course of the project, the Disk-shaped Compact Tension—DC(T)—test was chosen to be retained in the Illinois Tollway PRS and to be presented in this study for the design of crack-resistant mixtures. The DC(T) test was selected because of its high degree of correlation with field results and its excellent repeatability. Tailored Hamburg rut depth and stripping inflection point thresholds were also established for mainline and shoulder mixes.

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