Interactions of Nucleotide Bases with Decorated Si Surfaces from Molecular Dynamics Simulations

Abstract

b S Supporting Information ' INTRODUCTIONBiosensing devices such as DNA-based sensors, 1À9 which rely on the ability of single-stranded DNA probes, bound to an appropriately functionalized substrate, to recognize and capture the complementary DNA targets which move in solution, have become increasingly important in designing new biomedical detection systems 10À13 and finely tuned therapies. 14À16 These kinds of biosensors are essentially composed of a recognition and a transduction unit. The recognition unit usually consists of a solid-state inorganic support (i.e., gold, oxidized silicon, crystalline silicon, etc.) which is coated with a stable organic film (self-assembled monolayer, SAM) in order to tailor in a convenient way its properties and thus the characteristics of the interface. The organic monolayer can be further modified for DNA grafting. 17À19 The physical and chemical properties of the SAM covered surface are closely related to the structure of the SAM and to its specific attributes. In fact, thermal and chemical stability as well as surface polarity and hydrophobicity can have a strong impact upon nonspecific binding properties and could prevent DNA hybridization. Thus, an accurate investigation of the configuration and dynamics of the adsorbed chains might be important to understand the mechanisms which take place at the deposition interfaces and would help develop robust strategies for creating efficient and selective DNA-based devices. Notwithstanding monolayers have been characterized from an experimental point of view using different techniques including, for example, Fourier transform infrared (FT-IR) spectroscopy, 20 scanning tunneling microscopy (STM), 21,22 X-ray reflectivity, and atomic force microscopy (AFM); 23À25 only a small number of computational studies describing these systems at the atomic level have been reported to date. 22,26À30 Even fewer are the investigations which have used a classical all-atom molecular dynamics approach to estimate the free energy change upon adsorption of DNA strands at the aqueous SAM interface. 31À34 To the best of our knowledge, none of the cited works has examined in detail the adsorption and binding strength of single nucleotide bases on a decorated interface. Previous studies 35À38 showed that both single and double stranded DNA structures tethered to a functionalized substrate could adopt an upright orientation relative to the surface and swing randomly in the bulk region of the solvent or bend, twist, and tilt toward the interface, forming relatively stable hydrogen bonding interactions with the head groups of the SAM. As a matter of fact, the permanence of DNA bases near the substrate and the frequency of their contacts with the SAM are closely related to the DNA base sequence and the affinity of each single nucleotide base for the surface head groups. Indeed, once the bases reach the ABSTRACT: All-atom molecular dynamics simulations and potential of mean force calculations have been carried out to define a complete picture of the adsorpti...

Dispersion corrected DFT approaches for anharmonic vibrational frequency calculations: nucleobases and their dimers

“…DNA-based biosensors, for example, can consist of probes attached to functionalized substrates with the capability of recognizing and capturing specific DNA targets. In these hybrid systems, the nature of the interactions between purines/pyrimidines and the substrates is critical for the effective functionality of the devices and thus its characterization is a mandatory starting point for developing and improving high quality technologies [15][16][17][18][19][20] and finely tuned therapies 21,22 .…”

“…[9][10][11][12][13][14] DNAbased biosensors, for example, can consist of probes attached to functionalized substrates with the capability of recognizing and capturing specific DNA targets. In these hybrid systems, the nature of the interactions between purines/pyrimidines and the substrates is critical for the effective functionality of the devices and thus its characterization is a mandatory starting point for developing and improving high quality technologies [15][16][17][18][19][20] and finely tuned therapies. 21,22 Moreover, nucleic acid bases are powerful biomaterials for realizing rationally designed and functionally enhanced nanostructures for homogeneous dense surface coatings, bottom-up nanopatterning, and 3D nanoparticle lattices.…”

Complementary and partially complementary DNA duplexes tethered to a functionalized substrate: a molecular dynamics approach to biosensing

“…In order to get more insights about the individual surface binding properties of the nucleotide bases, an independent computational investigation was carried out. 51 Both potential of mean constraint force calculations and restrained/ unrestrained molecular dynamics simulations were used to determine the free energy change upon adsorption of the four nucleotide fragments and revealed that all the bases were attracted to the surface by electrostatic forces, had favorable free energy of binding and interacted with the layer through a balanced combination of electrostatic and van der Waals energy components. The approaching path was barrierless and stronger adsorptions were characterized by partial insertion of the fragments into the amine functionalizing substrate and by a large number of intermolecular hydrogen bonds.…”

Free energy landscapes of the encapsulation mechanism of DNA nucleobases onto carbon nanotubes

“…When the surface becomes hydrophilic, such as an amine functionalized Si (111) substrate, an opposite trend occurs and the pyrimidines exhibit higher binding affinities than the purine moieties. 30 The extreme narrowness of the nanotubes employed in the above studies precludes any possibility of molecular encapsulation. What happens when the diameter is increased, up to the point where the solid's internal volume is large enough to accommodate the nucleobases?…”