Predicting near-UV electronic circular dichroism in nucleosomal DNA by means of DFT response theory

Abstract

It is demonstrated that time-dependent density functional theory (DFT) calculations can accurately predict changes in near-UV electronic circular dichroism (ECD) spectra of DNA as the structure is altered from the linear (free) B-DNA form to the supercoiled N-DNA form found in nucleosome core particles. At the DFT/B3LYP level of theory, the ECD signal response is reduced by a factor of 6.7 in going from the B-DNA to the N-DNA form, and it is illustrated how more than 90% of the individual base-pair dimers contribute to this strong hypochromic effect. Of the several inter-base pair parameters, an increase in twist angles is identified as to strongly contribute to a reduced ellipticity. The present work provides first evidence that first-principles calculations can elucidate changes in DNA dichroism due to the supramolecular organization of the nucleoprotein particle and associates these changes with the local structural features of nucleosomal DNA.

Studying the excited electronic states of guanine rich DNA quadruples by quantum mechanical methods: main achievements and perspectives

“…The necessity of including a large number of chromophores makes at the moment unfeasible the application of Wave-Function based ab initio calculations. On the other hand, the results we report show that, when adopting a suitable functional, TD-DFT calculations, confirming the good performances obtained on DNA single and double strands, [70][71][72][73][74][75] well reproduce the effect of stacking geometry on the absorption and ECD spectra of G4s (Figure 2-4). 27,42 It is nowadays well assessed that the excited states in absorption are delocalized over multiple bases and that the coupling between the different chromophores is determined by the G4 conformation, giving account for the different ECD spectra.…”

VeloxChem: A Python‐driven density‐functional theory program for spectroscopy simulations in high‐performance computing environments

“…It has been demonstrated that ECD in linear and nucleosomal forms of DNA can be simulated by means of summing spectra from base‐pair dimers and thereby effectively transform the spectrum calculation of a large‐scale system into a large number of calculations for moderately sized systems . Similarly, ECD spectra of very short peptides and unfolded oligo‐peptides/proteins are in close agreement but, at the same time, the involvement of dynamic explicit water molecules in the electronic structures of accessible states makes the situation more complex and renders classical excitonic models unsuitable .…”

Steady-State Linear and Non-linear Optical Spectroscopy of Organic Chromophores and Bio-macromolecules

“…Their results show a very good agreement with the experimental CD fingerprint of the adenine-thymine base pairs homo-polymers in the near-ultraviolet region, corresponding to two positive bands at 260 and 283 nm and a more intense negative band at 249 nm. Furthermore, Norman et al ( 2015 ) tackled the case of the 147 base pairs long nucleosomal DNA (pdb code: 1KX5) employing a similar procedure. The results demonstrated the influence of the super-helical configuration on the CD spectra, including a hypsochromic shift of the band at 269 nm and a strong decrease of its intensity.…”