In silico molecular docking in DNA aptamer development

Navien, Tholasi Nadhan; Thevendran, Ramesh; Hamdani, Hazrina Yusof; Tang, Thean‐Hock; Citartan, Marimuthu

doi:10.1016/j.biochi.2020.10.005

Cited by 71 publications

(39 citation statements)

References 117 publications

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“…The number of hydrogen bonds was the highest, and it was the strongest force in the two combinations. These results indicated that myriocin could interact with NFYA and RIOK2 and form a stable complex [19], possibly explaining why NFYA and RIOK2 function was inhibited.…”

Section: Molecular Dockingmentioning

confidence: 86%

Comprehensive transcriptomic and proteomic analyses identify intracellular targets for myriocin to induce Fusarium oxysporum f. sp. niveum cell death

Wang

et al. 2021

Microb Cell Fact

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Background Myriocin is a natural product with antifungal activity and is derived from Bacillus amyloliquefaciens LZN01. Our previous work demonstrated that myriocin can inhibit the growth of Fusarium oxysporum f. sp. niveum (Fon) by inducing membrane damage. In this study, the antifungal actions of myriocin against Fon were investigated with a focus on the effects of myriocin on intracellular molecules. Results Analysis of DNA binding and fluorescence spectra demonstrated that myriocin can interact with dsDNA from Fon cells. The intracellular-targeted mechanism of action was also supported by transcriptomic and proteomic analyses; a total of 2238 common differentially expressed genes (DEGs) were identified. The DEGs were further verified by RT-qPCR. Most of the DEGs were assigned metabolism and genetic information processing functions and were enriched in ribosome biogenesis in eukaryotes pathway. The expression of some genes and proteins in ribosome biogenesis in eukaryotes pathway was affected by myriocin, primarily the genes controlled by the C6 zinc cluster transcription factor family and the NFYA transcription factor. Myriocin influenced the posttranscriptional processing of gene products by triggering the main RI (retained intron) events of novel alternative splicing; myriocin targeted key genes (FOXG_09470) or proteins (RIOK2) in ribosome biogenesis in eukaryotes pathway, resulting in disordered translation. Conclusions In conclusion, myriocin was determined to exhibit activity against Fon by targeting intracellular molecules. The results of our study may help to elucidate the antifungal actions of myriocin against Fon.

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Section: Molecular Dockingmentioning

confidence: 86%

Comprehensive transcriptomic and proteomic analyses identify intracellular targets for myriocin to induce Fusarium oxysporum f. sp. niveum cell death

Wang

et al. 2021

Microb Cell Fact

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“…To investigate the key motif of AES for increasing the peroxidase activity of myoglobin with the goal of obtaining advanced AESs with a stronger activity than that of the original N24-07, we conducted ‘ in silico maturation (ISM)’ ( 6 , 38 , 39 ) (Figure 2A ). ISM is our original strategy for the functional evolution of aptamers and has also recently been applied to improve the function of aptamers by other groups ( 50 , 51 ). To start the ISM, pre-selected aptamers, called ‘parent aptamers,’ are necessary.…”

Section: Resultsmentioning

confidence: 99%

G-quadruplex-forming aptamer enhances the peroxidase activity of myoglobin against luminol

Tsukakoshi

Yamagishi

Kanazashi

et al. 2021

Nucleic Acids Research

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Aptamers can control the biological functions of enzymes, thereby facilitating the development of novel biosensors. While aptamers that inhibit catalytic reactions of enzymes were found and used as signal transducers to sense target molecules in biosensors, no aptamers that amplify enzymatic activity have been identified. In this study, we report G-quadruplex (G4)-forming DNA aptamers that upregulate the peroxidase activity in myoglobin specifically for luminol. Using in vitro selection, one G4-forming aptamer that enhanced chemiluminescence from luminol by myoglobin's peroxidase activity was discovered. Through our strategy—in silico maturation, which is a genetic algorithm-aided sequence manipulation method, the enhancing activity of the aptamer was improved by introducing mutations to the aptamer sequences. The best aptamer conserved the parallel G4 property with over 300-times higher luminol chemiluminescence from peroxidase activity more than myoglobin alone at an optimal pH of 5.0. Furthermore, using hemin and hemin-binding aptamers, we demonstrated that the binding property of the G4 aptamers to heme in myoglobin might be necessary to exert the enhancing effect. Structure determination for one of the aptamers revealed a parallel-type G4 structure with propeller-like loops, which might be useful for a rational design of aptasensors utilizing the G4 aptamer-myoglobin pair.

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“…It is common practice to correct these structures in post. Image based on information contained within [27].…”

Section: In Silico Designmentioning

confidence: 99%

“…There are a number of programmes which are available for use in this field, some which are freely available and some requiring a subscription [28]. Irrespective of the programme used, the objective is to create a pose (two molecules which have formed a complex) with the lowest Gibbs free energy (∆G) binding energy [27]. Experiments themselves can take two main approaches, fixed or flexible docking which can be further sub-divided into 5 categories.…”

Section: In Silico Designmentioning

confidence: 99%

Development and validation of anti-human Alpha synuclein DNA aptamer using computer modelling techniques—an in silico study

Rock¹,

Zouganelis²,

Andrade³

et al. 2022

J. Integr. Neurosci.

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Background: Biomarker detection strategies have, in recent years, been moving towards nucleic acid-based detection systems in the form of aptamers, short oligonucleotide sequences which have shown promise in pre-clinical and research settings. One such aptamer is M5-15, a DNA aptamer raised against human alpha synuclein (α-syn) the causative agent in Lewy body and Parkinson's disease (PD) associated dementia. While this aptamer has shown promise, in silico methodologies have demonstrated a capacity to produce aptamers that have higher affinities for their targets than in vitro generated sequences. Methods: A Python script random generated library of DNA sequences were screened based on their thermodynamic stability with the use of DINAMelt server-QuickFold web server. The selected sequences were examined with MFold in order to generate secondary structure data that were used to produce 3D data with the use of RNA composer software. Further on, the structure was corrected and RNA was replaced with DNA and the virtual screening for α-syn aptamer took place with a series of molecular docking experiments with the use of CSD-Discovery-GOLD software. Results: Herein we propose an alternative in silico generated aptamer we call TMG-79 which demonstrates greater affinity for the target compared to M5-15 (M5-15 = -15.9 kcal/mol, TMG-79 = -17.77 kcal/mol) as well as better ChemPLP fitness scoring between the top poses . Structural analysis suggests that while there are similarities, the greater potential flexibility of TMG-79 could be promoting greater affinity for the α-syn compared to M5-15. Conclusions: In silico methods of aptamer generation has the potential to revolutionise the field of aptamer design. We feel that further development of TMG-79 and validation in vitro will make it a viable candidate for diagnostic and research use in the future.

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In silico molecular docking in DNA aptamer development

Cited by 71 publications

References 117 publications

Comprehensive transcriptomic and proteomic analyses identify intracellular targets for myriocin to induce Fusarium oxysporum f. sp. niveum cell death

Comprehensive transcriptomic and proteomic analyses identify intracellular targets for myriocin to induce Fusarium oxysporum f. sp. niveum cell death

G-quadruplex-forming aptamer enhances the peroxidase activity of myoglobin against luminol

Development and validation of anti-human Alpha synuclein DNA aptamer using computer modelling techniques—an in silico study

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