Vibrational Spectra of Nucleotides in the Presence of the Au Cluster Enhancer in MD Simulation of a SERS Sensor

Abstract

Surface-enhanced Raman scattering (SERS) nanoprobes have shown tremendous potential in in vivo imaging. The development of single oligomer resolution in the SERS promotes experiments on DNA and protein identification using SERS as a nanobiosensor. As Raman scanners rely on a multiple spectrum acquisition, faster imaging in real-time is required. SERS weak signal requires averaging of the acquired spectra that erases information on conformation and interaction. To build spectral libraries, the simulation of measurement conditions and conformational variations for the nucleotides relative to enhancer nanostructures would be desirable. In the molecular dynamic (MD) model of a sensing system, we simulate vibrational spectra of the cytosine nucleotide in FF2/FF3 potential in the dynamic interaction with the Au20 nanoparticles (NP) (EAM potential). Fourier transfer of the density of states (DOS) was performed to obtain the spectra of bonds in reaction coordinates for nucleotides at a resolution of 20 to 40 cm−1. The Au20 was optimized by ab initio density functional theory with generalized gradient approximation (DFT GGA) and relaxed by MD. The optimal localization of nucleotide vs. NP was defined and the spectral modes of both components vs. interaction studied. Bond-dependent spectral maps of nucleotide and NP have shown response to interaction. The marker frequencies of the Au20—nucleotide interaction have been evaluated.

MD Average of Vibrational Spectra of Nucleotides in a SERS Sensor Simulation with Varying Number of Au Nanoparticles

“…The present study uses MD simulation of the system consisting of the following components: nucleotide, Au NP (1 to 4 Au 20 pyramidal shaped NP), and single-layer graphene with a nanopore to translocate the nucleotide as seen in Figure 1. With the proven influence of the system components on the vibrational spectra of each part [43,44], the way to collect spectra of individual bonds into the spectra distinguishing each nucleotide and its methylated forms has been tested. The nucleotide vibrational frequencies were attributed to stretching, bending, or ring-breathing modes.…”

“…To resolve the interaction in the sensor, the time step was taken equal to 0.05 fsec with 32,768 steps (1.64 psec) for correlation evaluation at a few vibrational periods [48]. It provides the frequency resolution of vibrational modes at ∆f = 20 cm −1 and frequency interval length above 4000 cm −1 [42,43], which is comparable to the 15 cm −1 half-width of the Lorentzian function in the DFT calculation [49]. Collected single-bond spectra of For each atom in the bonds of the oligomer, the vibrational density of states (DOS) is calculated during translocation time through the graphene nanopore with attached Au NPs to accumulate all atomic spectra of the oligomer bonds.…”

“…Collected single-bond spectra of For each atom in the bonds of the oligomer, the vibrational density of states (DOS) is calculated during translocation time through the graphene nanopore with attached Au NPs to accumulate all atomic spectra of the oligomer bonds. The calculation method is described in detail in [43,44]. Because the interaction causes shift and/or intensity changes in selected vibration frequencies of the nucleotide spectra, the starting point and translocation speed were the same for each nucleotide and methylated form studied.…”

“…In our system, the 2D graphene nanopore is combined with a pyramidal Au nanoparticle (NP) (single vs. four identical pyramids) attached at the edge of the nanopore to form the SERS sensor. Such a design allows guiding the single oligomer through the created "hot" spot [42][43][44]. Individual bond spectra should be averaged to include contributions of multiple bonds into oligomer spectrum.…”