Molecular dynamics modeling of the sub-THz vibrational absorption of thioredoxin from E. coli

Abstract

Sub-terahertz (THz) vibrational modes of the protein thioredoxin in a water environment were simulated using molecular dynamics (MD) in order to find the conditions needed for simulation convergence, improve the correlation between experimental and simulated absorption frequencies, and ultimately enhance the predictive capabilities of computational modeling. Thioredoxin from E. coli was used as a model molecule for protocol development and to optimize the simulation parameters. The empirically parameterized software packages Amber 8 and 10 were used in this work. Using atomic trajectories from the constant energy and volume MD simulations, thioredoxin's sub-THz vibrational spectra and absorption coefficients were calculated in a quasi-harmonic approximation. An optimal production run length ~100 ps was found, in agreement with experimental data on thioredoxin relaxation dynamics. At the same time, a new procedure was developed for averaging correlation matrices of atomic coordinates in MD simulations. In particular, the open source package ptraj was edited to improve a matrix-analyzing function. Averaging only six matrices gave much more consistent results, with absorption peak intensities exceeding those from the individual spectra and a rather good correlation between simulated vibrational frequencies and experimental data.

Sub-THz Vibrational Spectroscopy of Bacterial Cells and Molecular Components

“…Nevertheless, rather good results were received for the protein thioredoxin fro m E. coli (see Fig. 19) after improving the convergence of simu lation [22], thus validating both, the experimental and theoretical results. Therefore, multip le resonances due to low frequency vibrational modes within biological macro molecules, co mponents of bacterial organis ms, are demonstrated in the sub-THz frequency range experiment ally in agreement with the theoretical pred iction.…”

“…Our MD simu lations were described in previous works [12,16,17] with the most detail analysis of procedures, protocols and parameters in the latest publication [22]. The obtained phonon modes can be convoluted to derive the far IR absorption spectrum of a mo lecule.…”

“…Our previous results on characterization of bio-mo lecules using Fourier transform (FT) spectroscopy detected mult iple resonances in transmission/absorption spectra of bio-molecules in the sub-THz frequency region [12][13][14]. Simu lations can help us to interpret the experimental data by assigning spectral features to specific molecu lar motions, and simultaneously with experimental characterizat ion co mputational modeling techniques have been developed using the energy min imization, normal mode analysis and mo lecular dynamics (MD) approaches to predict low frequency vibrational absorption spectra of short artificial DNA, and RNA [12,[15][16][17][18], large macro molecules of DNA [19,20] and proteins [21,22]. Direct comparison of experimental spectra with theoretical prediction for a short chain RNA frag ment with known structure showed reasonably good correlation [12,17] validating both experimental and theoretical results.…”

“…Some of cellu lar co mponents of E. co li, DNA, transfer RNA [20], and protein thioredoxin [21,22] were also characterized, and absorption spectra of relatively s mall macro molecules were simulated using MD. Vib rational frequencies from simu lated spectra for co mponents correlate rather well with the observed features.…”

Terahertz spectroscopy for bacterial detection: opportunities and challenges

“…Computational modeling techniques have been developed to understand and even to predict the spectral features of proteins and nucleic acids using the energy minimization, normal mode analysis, and molecular dynamics (MD) approaches. The reasonably good correlations clearly validate the experimental and theoretical results for tRNA (Bykhovski et al 2007), DNA (Globus et al 2013), and thioredoxin (Alijabbari et al 2012) from E. coli. Moreover, the predicted THz signature of Bacillus anthracis DNA was quite distinguishable from its simulants, B. subtilis DNA or E. coli DNA (Bykhovski et al 2005).…”