Molecular Dynamics Simulations of End-Tethered Single-Stranded DNA Probes on a Silica Surface

Wang, Zunliang; Zeng, Xin; Deng, Yan Xi; He, Nongyue; Wang, Qiong; Huang, Jianguo

doi:10.1166/jnn.2011.4994

Cited by 6 publications

(7 citation statements)

References 27 publications

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“…Despite the advantages of the microarray format, tethering oligonucleotides to a solid surface introduces constraints not present in solution-based assays. − Among these are nonspecific oligonucleotide-surface interactions and probe–probe crowding effects, both of which can affect hybridization efficiency and the ultimate assay sensitivity. Typical probe densities on a solid surface are on the order of 10 11 –10 13 /cm 2 , and the probes can thus be spaced close enough to interact with each other.…”

Section: Introductionmentioning

confidence: 99%

Molecular Crowding Effects on Microgel-Tethered Oligonucleotide Probes

Libera

2016

Langmuir

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Microgel tethering is a nontraditional method with which to bind oligonucleotide hybridization probes to a solid surface. Microgel-tethering physically positions the probes away from the underlying hard substrate and maintains them in a highly waterlike environment. This paper addresses the question of whether molecular crowding affects the performance of microgel-tethered molecular beacon probes. The density of probe-tethering sites is controlled experimentally using thin-film blends of biotin-terminated [PEG-B] and hydroxyl-terminated [PEG-OH] poly(ethylene glycol) from which microgels are synthesized and patterned by electron beam lithography. Fluorescence measurements indicate that the number of streptavidins, linear DNA probes, hairpin probes, and molecular beacon probes bound to the microgels increases linearly with increasing PEG-B/PEG-OH ratio. For a given tethering-site concentration, more linear probes can bind than structured probes. Crowding effects emerge during the hybridization of microgel-tethered molecular beacons but not during the hybridization of linear probes, as the tethering density increases. Crowding during hybridization is associated with conformational constraints imposed by the close proximity of closed and hybridized structured probes. The signal-to-background ratio (SBR) of hybridized beacons is highest and roughly constant for low tethering densities and decreases at the highest tethering densities. Despite differences between microgel tethering and traditional oligonucleotide surface-immobilization approaches, these results show that crowding defines an optimum tethering density for molecular beacon probes that is less than the maximum possible, which is consistent with previous studies involving various linear and structured oligonucleotide probes.

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Section: Introductionmentioning

confidence: 99%

Molecular Crowding Effects on Microgel-Tethered Oligonucleotide Probes

Libera

2016

Langmuir

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“…However, in the area of MD simulation on nucleic acid, other protocols have been frequently applied [32], [33], followed by the pioneering works [34]–[36]. In fact, the atom-based shifted force cutoff method has often been used [37]–[44], for which the efficiency has been dictated through the systematic and complete study by Norberg and Nilsson [30].…”

Section: Resultsmentioning

confidence: 99%

Molecular Dynamics Simulations of Double-Stranded DNA in an Explicit Solvent Model with the Zero-Dipole Summation Method

et al. 2013

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Molecular dynamics (MD) simulations of a double-stranded DNA with explicit water and small ions were performed with the zero-dipole summation (ZD) method, which was recently developed as one of the non-Ewald methods. Double-stranded DNA is highly charged and polar, with phosphate groups in its backbone and their counterions, and thus precise treatment for the long-range electrostatic interactions is always required to maintain the stable and native double-stranded form. A simple truncation method deforms it profoundly. On the contrary, the ZD method, which considers the neutralities of charges and dipoles in a truncated subset, well reproduced the electrostatic energies of the DNA system calculated by the Ewald method. The MD simulations using the ZD method provided a stable DNA system, with similar structures and dynamic properties to those produced by the conventional Particle mesh Ewald method.

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“…In the MNPs-CL system, the amino-modified probes were immobilized onto carboxylated MNPs and then hybridized with target DNA for CL detection after magnetic separation, which is currently one of new focuses in biological detection 56 - 59 . This system had been well developed in many studies, especially those involving original works from our laboratory 48 , 60 , 61 , 62 , 63 . Various experimental parameters had been optimized, including the MNPs amounts, carboxyl concentration to amino-MNPs, concentration of specific amino-probes, hybridization temperature and time, and so on.…”

Section: Discussionmentioning

confidence: 99%

“…The result from the optimization of hybridization probes suggested that the structure of DNA molecules (probes length, binding site, and so on) tethered to surfaces might significantly have affected the hybridization efficiency. The dynamics and interaction of DNA probes tethered on the silica surface could be investigated by a molecular dynamics simulation, which was helpful to better optimize the DNA probes design 63 . The simulation was performed by use of the CHARMM software package with CHARMM27 force field 64 , 65 , and the resulting system was subjected to a series of minimizations through the CHARMM program 66 .…”

Section: Discussionmentioning

confidence: 99%

Copy Number Variation Analysis by Ligation-Dependent PCR Based on Magnetic Nanoparticles and Chemiluminescence

Liu¹,

Hu²,

Zhang

et al. 2015

Theranostics

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A novel system for copy number variation (CNV) analysis was developed in the present study using a combination of magnetic separation and chemiluminescence (CL) detection technique. The amino-modified probes were firstly immobilized onto carboxylated magnetic nanoparticles (MNPs) and then hybridized with biotin-dUTP products, followed by amplification with ligation-dependent polymerase chain reaction (PCR). After streptavidin-modified alkaline phosphatase (STV-AP) bonding and magnetic separation, the CL signals were then detected. Results showed that the quantification of PCR products could be reflected by CL signal values. Under optimum conditions, the CL system was characterized for quantitative analysis and the CL intensity exhibited a linear correlation with logarithm of the target concentration. To validate the methodology, copy numbers of six genes from the human genome were detected. To compare the detection accuracy, multiplex ligation-dependent probe amplification (MLPA) and MNPs-CL detection were performed. Overall, there were two discrepancies by MLPA analysis, while only one by MNPs-CL detection. This research demonstrated that the novel MNPs-CL system is a useful analytical tool which shows simple, sensitive, and specific characters which are suitable for CNV analysis. Moreover, this system should be improved further and its application in the genome variation detection of various diseases is currently under further investigation.

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Molecular Dynamics Simulations of End-Tethered Single-Stranded DNA Probes on a Silica Surface

Cited by 6 publications

References 27 publications

Molecular Crowding Effects on Microgel-Tethered Oligonucleotide Probes

Molecular Crowding Effects on Microgel-Tethered Oligonucleotide Probes

Molecular Dynamics Simulations of Double-Stranded DNA in an Explicit Solvent Model with the Zero-Dipole Summation Method

Copy Number Variation Analysis by Ligation-Dependent PCR Based on Magnetic Nanoparticles and Chemiluminescence

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