Molecular dynamics simulation as a promising approach for computational study of liquid crystal-based aptasensors.

As a potent computational methodology, molecular dynamics (MD) simulation provides advantageous knowledge about biological compounds from the molecular viewpoint. In particular, MD simulation gives exact information about aptamer strands, such as the short synthetic oligomers, their orientation, binding sites, folding-unfolding state, and conformational re-arrangement. Also, the effect of the different chemicals and biochemicals as the components of aptamer-based sensors (aptasensors) on the aptamer-target interaction can be investigated by MD simulation. Liquid crystals (LCs) as soft substances with characteristics of both solid anisotropy and liquid fluidity are new candidates for designing label-free aptasensors. To now, diverse aptasensors have been developed experimentally based on the optical anisotropy, fluidity, and long-range orientational order of LCs. Here, we represent a computational model of an LC-based aptasensor through a detailed MD simulation study. The different parameters are defined and studied to achieve a comprehensive understanding of the computational design of the LC-based aptasensor, including the density of LCs, their orientation angle, and lognormal distribution in the absence and presence of aptamer strands, both aptamer and target molecules with various concentrations, and interfering substance. As a case study, the tobramycin antibiotic is considered the target molecule for the computational model of the LC-based aptasensor.Communicated by Ramaswamy H. Sarma.

Reducing the assemblies of amyloid-beta multimers by sodium dodecyl sulfate surfactant at concentrations lower than critical micelle concentration: molecular dynamics simulation exploration.

Amyloid-ß peptide, the predominant proteinaceous component of senile plaques, is responsible for the incidence of Alzheimer's disease (AD), an age-associated neurodegenerative disorder. Specifically, the amyloid-ß(1-42) (Aß1-42) isoform, known for its high toxicity, is the predominant biomarker for the preliminary diagnosis of AD. The aggregation of the Aß1-42 peptides can be affected by the components of the cellular medium through changing their structures and molecular interactions. In this study, we investigated the effect of sodium dodecyl sulfate (SDS) at much lower concentrations than the critical micelle concentration (CMC) on Aß1-42 aggregation. For this purpose, we studied mono-, di-, tri- and tetramers of Aß1-42 peptide in two different concentrations of SDS molecules (10 and 40 molecules) using a 300 ns molecular dynamics simulation for each system. The distance between the center of mass (COM) of Aß1-42 peptides confirms that an increase in the number of SDS molecules decreases their aggregation probability due to greater interaction with SDS molecules. Besides, the less compactness parameter reveals the reduced aggregation probability of Aß1-42 peptides. Based on the energetic FEL landscapes, SDS molecules with the concentration closer to the CMC are an effective inhibitory agent to prevent the formation of Aß1-42 fibrils. Also, the aggregation direction of the peptide pairs can be predicted by determining the direction of the accumulation-deterrent forces.Communicated by Ramaswamy H. Sarma.

A simple and robust aptasensor assembled on surfactant-mediated liquid crystal interface for ultrasensitive detection of mycotoxin.

Here, a simple aptasensing approach is represented to sensitively detect ochratoxin A (OTA) as one of the most perilous mycotoxins with carcinogenic, nephrotoxic, teratogenic, and immunosuppressive sequels on human health. The aptasensor is based on the alteration in the orientational order of liquid crystal (LC) molecules at the surfactant-arranged interface. Homeotropic alignment of LCs is achieved by the interaction of the surfactant tail with LCs. By perturbing the alignment of LCs due to the electrostatic interaction of the aptamer strand with the surfactant head, a colorful polarized view of the aptasensor substrate is induced drastically. While OTA causes the re-orientation of LCs to a vertical state by forming an OTA-aptamer complex that induces darkness of the substrate. This study shows that the length of the aptamer strand impacts the efficiency of the aptasensor; longer strand results in the greater disruption of LCs, and therefore, increases the aptasensor sensitivity. Hence, the aptasensor can determine OTA in the linear concentration range of 0.1 fM-1 pM as low as 0.021 fM. The aptasensor is capable to monitor OTA in grape juice, coffee drink, corn, and human serum real samples. The proposed LC-based aptasensor provides a cost-effective, easy-to-carry, operator-independent, and user-friendly array with great potential to develop portable sensing gadgets for food quality control and health care monitoring.

Exonuclease-based aptasensors: Promising for food safety and diagnostic aims.

As of today's requirement, developing cost-effective smart sensing tools with ultrahigh sensitivity for food safety insurance is of special importance. For this purpose, aptamer-based biosensors (aptasensors) powered by the superiorities of the recycling signal amplification strategies have been expanded especially. Target recycling supported by enzymes is an appealing approach for implementing signal amplification. As the supreme biocatalyst enzymes, exonucleases can inaugurate signal improvement by involving a single target in a process would result in appreciable repeating cycles of the cleavage of the phosphodiester bonds between the building blocks of the nucleic acid strands, and also, their terminals. Although there are diverse substances for catalyzing amplification strategies, including nanoparticles, carbon-based nanocomposites, and quantum dots (QDs), exonucleases are of superiority over them by simplifying the amplification process with no need for the complicated pre-treatment processes. The outstanding selectivity and great sensitivity of the aptasensors tuned by amplification potency of exonucleases nominate them as the promising sensing tools for label-free, ease-of-use, cost-effective, and real-time diagnosis of diverse targets. Here, we summarize the achievements and perspectives in the scientific branch of aptasensor design for the qualitative monitoring of diverse targets by cooperation of exonucleases with the conspicuous potential for the signal amplification. Finally, some results are expressed to provide a comprehensive viewpoint for developing novel nuclease-based aptasensors in the future.

A tag-free fluorescent aptasensor for tobramycin detection using a hybridization of three aptamer strands and SYBR Green I dye.

In this study, a sensitive fluorescent method is designed to detect tobramycin (TOB) drug applying a hybrid structure of three aptamer strands and SYBR Green I (SGI) fluorescent dye as the bioreceptor segment and signal indicator, respectively. The preferential binding of the aptamers to TOB resulted in the collapse of the hybridized aptamer skeleton to the single strands. So, the intercalation of SGI molecules reduced that quenched the fluorescence response. The aptasensing assay provided the superior target specificity with a detection limit (LOD) of 0.153 pM and a wide linear dynamic range over 0.5 pM-300 µM. The aptasensor could successfully quantify TOB in human serum samples. The tag-free sensor with the remarkable advantages of simplicity, easy-to-use, cost-effectiveness, and high sensitivity is superior to be applicable for clinical samples.

A comprehensive computer simulation insight into inhibitory mechanisms of EGCG and NQTrp ligands on amyloid-beta assemblies as the Alzheimer's disease insignia.

Amyloid-ß peptide with predominant presence in the senile plaques is the most common agent for Alzheimer's disease (AD) incidence. Assembly of the amyloid-ß(1-42) (Aß1-42) isoform is known as the main reason for the AD appearance. Epigallocatechin gallate (EGCG) and 1,4-naphthoquinone-2-yl-L-tryptophan (NQTrp) are two small molecules that inhibit the formation of the Aß1-42 fibrils. The present study provides molecular insight to clarify the inhibitory mechanisms of the EGCG and NQTrp ligands on the Aß1-42 assemblies by using molecular dynamics (MD) simulation. Hence, nine different Aß1-42-containing systems including the monomer, dimer, and hexamer of Aß1-42 considering each of them in a media with no ligands, in the presence of one EGCG ligand, and in the presence of one EGCG ligand were studied with a simulation time of 1 µs for each system. The precise investigation of the peptide-ligand distance, conformational factor (Pi), solvent accessible surface area (SASA), dictionary of secondary structure (DSSP), and Lys28-Ala42 salt bridge analyses confirmed that the hydroxyl-rich structure of the EGCG ligand applied its inhibitory effect on the aggregation of the peptides indirectly by involving water molecules. While the hydroxyl-free structure of the NQTrp ligand exposed its inhibitory effect through a direct interaction with the Aß1-42 peptides. Besides, reduced density gradient (RDG) analysis clarified the hydrogen bonding interactions as the dominant ones for the peptide-EGCG systems, and also, steric and van der Waals interactions for the peptide-NQTrp systems.Communicated by Ramaswamy H. Sarma.

A label-free liquid crystal-assisted aptasensor for trace level detection of tobramycin in milk and chicken egg samples.

Developed herein is an aptasensing array based on liquid crystal (LC) for monitoring of tobramycin (TOB) antibiotic. The direction of LC molecules from vertical to a random status was induced by the conformational changes of the specific aptamer due to its selective interaction with the target. The dark view of the aptasensing platform changed to colorful through observation by a polarized light microscope that clarifies the TOB presence. The aptasensor is especially able to determine TOB in the linear concentration range of 0.005-600 pM with a limit of detection (LOD) as 0.0021 pM. The TOB values can be determined successfully in the milk and chicken egg samples that highlights the potential applicability of the designed aptasensor. The proposed sensing approach is facile, operator-independent, label-free, and ultra-sensitive, making it novel for developing real-time portable sensing devices for future.

A fluorescence imaging-supported aptasensor for sensitive monitoring of cadmium pollutant in diverse samples: A critical role of metal organic frameworks.

Water pollution, as the remarkable environmental remediation issue, is a today worldwide concern. Cadmium ion (Cd2+) as a hazardous water pollutant is seriously detrimental to human health, food safety, and ecological areas. Hence, we successfully designed a simple detection array for monitoring of ultra-low levels of Cd2+ ion by combining the advantages of aptamer as a high sensitive and selective sensing probe and zeolitic imidazolate framework-8 (ZIF-8) as a superior fluorescence quenching inducer. To have a portable and on-site detection assay, the aptamer biosensing array (aptasensor) was designed by using a paper-supported substrate. The basis of the designed paper-supported aptasensor was the specific complexation of Cd2+ with the aptamer strand, adsorption of fluorescein-labeled complementary (FAM-CP) strand on the ZIF-8 surface, and fluorescence quenching of FAM molecule after the leakage of the injected target solution on the sample zone of the paper substrate to the detection part. A linear relationship was obtained between the Mean Gray Value index, as a criterion for the fluorescence quenching, and the Cd2+ concentration in the range of 0.1-120 pM with a detection limit of 0.076 pM. The aptasensor could detect Cd2+ in the diverse real sample, including tap water, milk, coffee, and human blood serum.

Recent Advances in Aptasensing Strategies for Monitoring Phycotoxins: Promising for Food Safety.

Phycotoxins or marine toxins cause massive harm to humans, livestock, and pets. Current strategies based on ordinary methods are long time-wise and require expert operators, and are not reliable for on-site and real-time use. Therefore, it is urgent to exploit new detection methods for marine toxins with high sensitivity and specificity, low detection limits, convenience, and high efficiency. Conversely, biosensors can distinguish poisons with less response time and higher selectivity than the common strategies. Aptamer-based biosensors (aptasensors) are potent for environmental monitoring, especially for on-site and real-time determination of marine toxins and freshwater microorganisms, and with a degree of superiority over other biosensors, making them worth considering. This article reviews the designed aptasensors based on the different strategies for detecting the various phycotoxins.