Modeling the Infrared Spectroscopy of Oligonucleotides with ¹³C Isotope Labels

Abstract

The carbonyl stretching modes have been widely used in linear and two-dimensional infrared (IR) spectroscopy to probe the conformation, interaction, and biological functions of nucleic acids. However, due to their universal appearance in nucleobases, the IR absorption bands of nucleic acids are often highly congested in the 1600–1800 cm–1 region. Following the fruitful applications in proteins, 13C isotope labels have been introduced to the IR measurements of oligonucleotides to reveal their site-specific structural fluctuations and hydrogen bonding conditions. In this work, we combine recently developed frequency and coupling maps to develop a theoretical strategy that models the IR spectra of oligonucleotides with 13C labels directly from molecular dynamics simulations. We apply the theoretical method to nucleoside 5′-monophosphates and DNA double helices and demonstrate how elements of the vibrational Hamiltonian determine the spectral features and their changes upon isotope labeling. Using the double helices as examples, we show that the calculated IR spectra are in good agreement with experiments and the 13C isotope labeling technique can potentially be applied to characterize the stacking configurations and secondary structures of nucleic acids.

Ultrafast Spectroscopy Reveals Slow Water Dynamics in Biocondensates

“…Dynamics around the AMP ring mode were also slowed between the dilute and condensate phases from 0.78 to 1.56 ps, respectively. As AMP and arginine both interact via cation–pi and pi–pi- stacking, the slowdown observed is likely a result of a combination of these interactions, but experiments cannot disentangle these interactions; additionally, the mechanisms underlying the slowdown of AMP are difficult to pinpoint due to the delocalized nature of the ring mode, unlike the amide I mode. , …”

“…As AMP and arginine both interact via cation−pi and pi−pi-stacking, the slowdown observed is likely a result of a combination of these interactions, but experiments cannot disentangle these interactions; additionally, the mechanisms underlying the slowdown of AMP are difficult to pinpoint due to the delocalized nature of the ring mode, unlike the amide I mode. 50,51 The measured 2D IR relaxation times are driven primarily by the fluctuations of the H-bond network, since H-bond switching is a three-body process that requires proper orientation of waters for the jump to take place, disrupted H-bond networks lead to longer C�O�water H-bond lifetimes. 52,53 Though the modes measured by 2D IR are delocalized over several oscillators, the local fluctuations of the individual oscillators are reported by the time evolution of the 2D IR lineshapes.…”

Accelerated Bayesian Inference for Molecular Simulations using Local Gaussian Process Surrogate Models

“…Molecular simulations are able to estimate a broad array of complex experimental observables, including scattering patterns from neutron and X-ray sources and spectra from near-infrared, terahertz, sum frequency generation, , and nuclear magnetic resonance . Recent interest in these experiments to study hydrogen bonding networks of water at interfaces, , electrolyte solutions, and biological systems has motivated the continued advancement of simulations to calculate these properties from first-principles. − However, the ability to estimate these complex properties comes with a high computational cost. This barrier greatly limits our ability to quantify how experimental, model, and parametric uncertainty impact molecular simulation predictions, making it difficult to know whether a model is an appropriate representation of nature or if it is simply overfitting to a given training set.…”

“…Molecular simulations are able to estimate a broad array of complex experimental observables, including scattering patterns from neutron and X-ray sources and spectra from nearinfrared, 1 terahertz, 2 sum frequency generation, 3,4 and nuclear magnetic resonance. 5 Recent interest in these experiments to study hydrogen bonding networks of water at interfaces, 6,7 electrolyte solutions, 8 and biological systems 9 has motivated the continued advancement of simulations to calculate these properties from first-principles. 10−12 However, the ability to estimate these complex properties comes with a high computational cost.…”