The assessment of three dimensional modelling design for single strand DNA aptamers for computational chemistry application

Sabri, M.; Hamid, Azzmer Azzar Abdul; Hitam, Sharifah Mariam Sayed; Rahim, Mohd. Zulkhairi Abdul

doi:10.1016/j.bpc.2020.106492

Cited by 29 publications

(15 citation statements)

References 31 publications

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“…The LNA aptamer (2PN9) had a simpler three-dimensional structure mainly due to its small size (16 nucleotides), probably justifying its lower RMSD. Similar RMSD values were reported for DNA aptamers and their experimentally deposited structures by other in silico workflows [ 13 , 19 ].…”

Section: Resultssupporting

confidence: 82%

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Modelling aptamers with nucleic acid mimics (NAM): From sequence to three-dimensional docking

et al. 2022

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Aptamers are single-stranded oligonucleotides, formerly evolved by Systematic Evolution of Ligands by EXponential enrichment (SELEX), that fold into functional three-dimensional structures. Such conformation is crucial for aptamers’ ability to bind to a target with high affinity and specificity. Unnatural nucleotides have been used to develop nucleic acid mimic (NAM) aptamers with increased performance, such as biological stability. Prior knowledge of aptamer-target interactions is critical for applying post-SELEX modifications with unnatural nucleotides since it can affect aptamers’ structure and performance. Here, we describe an easy-to-apply in silico workflow using free available software / web servers to predict the tertiary conformation of NAM, DNA and RNA aptamers, as well as the docking with the target molecule. Representative 2ʹ-O-methyl (2ʹOMe), locked nucleic acid (LNA), DNA and RNA aptamers, with experimental data deposited in Protein Data Bank, were selected to validate the workflow. All aptamers’ tertiary structure and docking models were successfully predicted with good structural similarity to the experimental data. Thus, this workflow will boost the development of aptamers, particularly NAM aptamers, by assisting in the rational modification of specific nucleotides and avoiding trial-and-error approaches.

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Section: Resultssupporting

confidence: 82%

“…Moreover, most computational tools have been designed for RNA; thus, having to be adapted to predict the tertiary structure of single-stranded DNA. Additionally, they are either unable to address NAM and/or require specialized computational and molecular modelling skills to use them [ 13 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Modelling aptamers with nucleic acid mimics (NAM): From sequence to three-dimensional docking

et al. 2022

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“…The simulation condition was set at the room temperature (300 K) and the atmospheric pressure (1 bar) to closely mimic the general experiment conditions. The NVT thermal equilibration was carried out with a constrained structure and a velocity rescale thermostat specific to GROMACS, followed by NPT pressure equilibration was applied with the same velocity-rescale temperature coupling in addition to the Parrinello−Rahman pressure coupling [ 85 ]. The fully temperature and pressure equilibrated system was then used as the initial configuration for the MD production dynamic analysis.…”

Section: Methodsmentioning

confidence: 99%

Computational Screening for the Anticancer Potential of Seed-Derived Antioxidant Peptides: A Cheminformatic Approach

et al. 2021

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Some seed-derived antioxidant peptides are known to regulate cellular modulators of ROS production, including those proposed to be promising targets of anticancer therapy. Nevertheless, research in this direction is relatively slow owing to the inevitable time-consuming nature of wet-lab experimentations. To help expedite such explorations, we performed structure-based virtual screening on seed-derived antioxidant peptides in the literature for anticancer potential. The ability of the peptides to interact with myeloperoxidase, xanthine oxidase, Keap1, and p47phox was examined. We generated a virtual library of 677 peptides based on a database and literature search. Screening for anticancer potential, non-toxicity, non-allergenicity, non-hemolyticity narrowed down the collection to five candidates. Molecular docking found LYSPH as the most promising in targeting myeloperoxidase, xanthine oxidase, and Keap1, whereas PSYLNTPLL was the best candidate to bind stably to key residues in p47phox. Stability of the four peptide-target complexes was supported by molecular dynamics simulation. LYSPH and PSYLNTPLL were predicted to have cell- and blood-brain barrier penetrating potential, although intolerant to gastrointestinal digestion. Computational alanine scanning found tyrosine residues in both peptides as crucial to stable binding to the targets. Overall, LYSPH and PSYLNTPLL are two potential anticancer peptides that deserve deeper exploration in future.

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“…It is worth stressing that the quality of docking simulations with the use of software packages such as DOCK6.9, AutoDock Vina, ZDOCK, HADDOCK, or rDock depends on the accuracy of 2D and 3D aptamer structure prediction [ 100 , 101 , 102 ]. Regrettably, structural studies for aptamer–ligand interactions are still the bottleneck in this field, as both X-ray crystallography and NMR are challenging techniques to employ since the experimental determination of 3D DNA or RNA structures is notoriously difficult [ 103 , 104 , 105 ]. Inaccuracies due to the lack of structural data on aptamers and the conformations they adopt when complexed with their ligands are further aggravated by the fact that most of the docking algorithms have been initially developed for proteins and protein–protein interactions [ 106 ].…”

Section: Nucleic Acid Aptamersmentioning

confidence: 99%

Electrochemical Aptasensors for Antibiotics Detection: Recent Achievements and Applications for Monitoring Food Safety

Evtugyn

Porfireva

Tsekenis

et al. 2022

Sensors

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Antibiotics are often used in human and veterinary medicine for the treatment of bacterial diseases. However, extensive use of antibiotics in agriculture can result in the contamination of common food staples such as milk. Consumption of contaminated products can cause serious illness and a rise in antibiotic resistance. Conventional methods of antibiotics detection such are microbiological assays chromatographic and mass spectroscopy methods are sensitive; however, they require qualified personnel, expensive instruments, and sample pretreatment. Biosensor technology can overcome these drawbacks. This review is focused on the recent achievements in the electrochemical biosensors based on nucleic acid aptamers for antibiotic detection. A brief explanation of conventional methods of antibiotic detection is also provided. The methods of the aptamer selection are explained, together with the approach used for the improvement of aptamer affinity by post-SELEX modification and computer modeling. The substantial focus of this review is on the explanation of the principles of the electrochemical detection of antibiotics by aptasensors and on recent achievements in the development of electrochemical aptasensors. The current trends and problems in practical applications of aptasensors are also discussed.

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The assessment of three dimensional modelling design for single strand DNA aptamers for computational chemistry application

Cited by 29 publications

References 31 publications

Modelling aptamers with nucleic acid mimics (NAM): From sequence to three-dimensional docking

Modelling aptamers with nucleic acid mimics (NAM): From sequence to three-dimensional docking

Computational Screening for the Anticancer Potential of Seed-Derived Antioxidant Peptides: A Cheminformatic Approach

Electrochemical Aptasensors for Antibiotics Detection: Recent Achievements and Applications for Monitoring Food Safety

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