Challenges in Simulating Light-Induced Processes in DNA

Abstract

In this contribution, we give a perspective on the main challenges in performing theoretical simulations of photoinduced phenomena within DNA and its molecular building blocks. We distinguish the different tasks that should be involved in the simulation of a complete DNA strand subject to UV irradiation: (i) stationary quantum chemical computations; (ii) the explicit description of the initial excitation of DNA with light; (iii) modeling the nonadiabatic excited state dynamics; (iv) simulation of the detected experimental observable; and (v) the subsequent analysis of the respective results. We succinctly describe the methods that are currently employed in each of these steps. While for each of them, there are different approaches with different degrees of accuracy, no feasible method exists to tackle all problems at once. Depending on the technique or combination of several ones, it can be problematic to describe the stacking of nucleobases, bond breaking and formation, quantum interferences and tunneling or even simply to characterize the involved wavefunctions. It is therefore argued that more method development and/or the combination of different techniques are urgently required. It is essential also to exercise these new developments in further studies on DNA and subsystems thereof, ideally comprising simulations of all of the different components that occur in the corresponding experiments.

Multireference Approaches for Excited States of Molecules

“…and ADC(2): tUra 827,828 ), and kinetics (CASPT2: aza-tThy+O2 629 829 Computations studying these phenomena and the challenges present have been reviewed extensively in recent articles. 720,830 For multireference computations not only the general size of the system is demanding, but it is also particularly challenging to maintain a balanced distribution of the active orbitals over the involved nucleobases. Therefore, SR methods such as DFT/TDDFT 720,[831][832][833] and CC/ADC 188,738,834,835 have been the main workhorse in this field, and only a smaller number of MR computations have been performed.…”

Neural networks and kernel ridge regression for excited states dynamics of CH2NH 2+ : From single-state to multi-state representations and multi-property machine learning models

“…In this way, large molecules, i.e., with up to hundreds of atoms, can still be treated. Still, a lot of electronic structure calculations are necessary and the latter represent an important bottleneck limiting the simulation times of nonadiabatic dynamics to the range of femto-to picoseconds [13][14][15][16].…”

Electronic Relaxation Dynamics of UV-Photoexcited 2-Aminopurine–Thymine Base Pairs in Watson–Crick and Hoogsteen Conformations

“…However, understanding the complex electronic relaxation mechanisms in photoexcited oligonucleotides continues to present challenges due to competing intra-strand deactivation dynamics induced via charge-transfer and stacking interactions, including exciton and excimer formation, and inter-strand de-excitation via H-bonded base pairs. [25][26][27][28][29][30] Moreover, as recently discovered, duplex DNA also contains transient Hoogsteen base pairs as additional structural motifs to enhance functional versatility beyond the Watson-Crick limitations, 31,32 further complicating the dynamics of photoexcited DNA, especially when containing 2AP.…”