Computing the electronic circular dichroism spectrum of DNA quadruple helices of different topology: A critical test for a generalized excitonic model based on a fragment diabatization. Issue 5 (12th February 2023)

• Record Type: Journal Article
• Authors: Asha, Haritha; Green, James A.; Esposito, Luciana; Santoro, Fabrizio; Improta, Roberto
• Is Part Of: Chirality. Volume 35:Issue 5(2023)
• Page Start: 298
• Page End: 310
• Publication Date: 2023-02-12
• Subjects: ECD -- excitonic model -- fragment diabatization -- guanine quadruplexes; Chirality -- Periodicals; Pharmaceutical chemistry -- Periodicals; 541.22
• DOI: 10.1002/chir.23540
• Languages: English
• ISSNs: 0899-0042

Abstract

Abstract: In this study, we exploit a recently developed fragment diabatization‐based excitonic model, FrDEx, to simulate the electronic circular dichroism (ECD) spectra of three guanine‐rich DNA sequences arranged in guanine quadruple helices with different topologies: thrombin binding aptamer (antiparallel), c‐Myc promoter (parallel), and human telomeric sequence (3+1 hybrid). Starting from time‐dependent density functional theory (TD‐DFT) calculations with the M052X functional, we apply our protocol to parameterize the FrDEX Hamiltonian, which accounts for electron density overlap and includes both the coupling with charge transfer transitions and the effect of the surrounding bases on the local excitation of each chromophore. The TD‐DFT/M052X spectral shapes are in good agreement with the experimental ones, the main source of discrepancy being related to the intrinsic error on the computed transition energies of guanine monomer. FrDEx spectra are fairly close to the reference TD‐DFT ones, allowing a significant advance with respect to a more standard excitonic Hamiltonian. We also show that the ECD spectra are sensitive to the inclusion of the inner K + cation in the calculation. Abstract : The prediction of the electronic circular dichroism (ECD) of complex molecular structures with strongly interacting chromophores is a hot topic in biology and material science. Here we test on different guanine quadruple helices the performance of a protocol we recently proposed based on a fragment diabatization and a generalized excitonic.