Sensors for DNA detection: theoretical investigation of the conformational properties of immobilized single-strand DNA

Abstract

A major challenge in the design and creation of biomolecular sensors is the development of efficient strategies using both existing synthetic technologies and novel fabrication methods to effectively adsorb and assemble different molecular species on suitable substrates. In order to generate stable and effective biodevices it is fundamental to understand the mechanisms responsible for the formation of the supramolecular structures, to evaluate to what extent the function and conformation of the adsorbed macromolecules are influenced by their interactions with the substrates and the environment and to identify possible causes of disruption, with the ultimate aim of suggesting and selecting appropriate methodologies to design highly efficient systems. Here in silico modeling comes into play, provided that realistic models and reliable computational strategies are employed. This paper is focused on DNA detection systems based on the hybridization between a DNA target and its complementary probe, which is present either in solution or on a solid support. MD simulations of the fully hydrated single strand attached to an allylamine functionalized Si(111) surface in aqueous solution are presented. A reliable and high quality picture of the structural flexibility and dynamic properties of the modified and unmodified DNA segment in solution together with the ability of DNA to rearrange its structure due to environmental effects is given and clarified.

Joyce and Ulysses: integrated and user-friendly tools for the parameterization of intramolecular force fields from quantum mechanical data

“…In fact, there are several cases in which the invoked transferability does not warrant sufficient accuracy for the description of molecular structure and interactions, thus undermining the reliability of the simulation results. This problem may concern the reproduction of spectroscopic properties, 30,36,37 a correct assessment of the delicate balance of inter-and intra-molecular forces that leads to liquid crystalline transitions 38 or other supramolecular assemblies, 39 the description of the changes in flexibility and molecular shape of large (bio-)molecules upon novel functionalizations, [40][41][42][43][44][45] the extension of FFs to excited electronic states. [46][47][48][49][50][51] One possible route to overcome these problems is to specifically re-parameterize only some terms of the adopted FF, 20,[52][53][54] such as point charges or torsional energy profiles of the most flexible ''soft'' dihedrals, the latter being more sensitive to molecular details with respect to the ''stiff'' stretching or bending internal coordinates (ICs).…”

Parameterization and validation of an accurate force-field for the simulation of alkylamine functionalized silicon (111) surfaces

“…35 Amino groups are indeed easy to prepare, have stable functionality and wide applicability but, even if their mono-layers were characterized using different experimental techniques, still relatively little is known about their overall structure, including packing and coverage. Based on the work of Pack et al, 35,36 allylamine molecules were selected for our studies and recent molecular dynamics (MD) simulations were performed by our group 37 to investigate the conformational behavior of a single strand of DNA immobilized on a propyl-amine functionalized Si(111) surface. In particular, in the aforementioned MD simulations, 100% coverage was employed.…”

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

“…21 The validity of all-atom molecular dynamics to simulate the hybridization process of the end-tethered DNA single strand, the intermediate structures appeared during the formation of the double helix, their internal dynamics and their behavior with respect to the substrate was demonstrated by Monti et al, 22 who also studied the conformation behavior of the fully hydrated single strand tethered to an allylamine functionalized Si(111) surface in aqueous solution using MD simulations. 23 It is interesting to note that, although these previous simulations reported many aspects of the dynamical behavior of DNA molecules tethered to a surface, information about the interactions between neighboring DNA molecules has not been revealed completely because only one DNA molecule (single strand or double strand) was considered in the simulation box per unit cell in these studies, so that the interaction between the surface-tethered neighboring DNA molecules is mainly based on interactions between DNA and its periodic images. Recently, Lee and Schatz studied the interaction between neighboring DNA duplexes having the same base pair composition on a flat gold surface using MD simulations.…”

“…[15][16][17][18] From a theoretical point of view, both all-atomistic (high resolution) and coarse-grained (low resolution) models have been used to describe the dynamical behavior of DNA strands tethered to a surface and their hybridization process. [19][20][21][22][23][24][25][26][27] Wong and Pettitt performed all-atom MD simulations to characterize the conformation change of a 12-mer double-stranded DNA (dsDNA) tethered to a neutral, epoxide coated silica surface in their pioneer work. [19][20] They found the dsDNA on the surface has both upright and tilted conformations.…”