Reaction Path Averaging: Characterizing the Structural Response of the DNA Double Helix to Electron Transfer

A polarizable environment, prominently the solvent, responds to electronic changes in biomolecules rapidly. The knowledge of conformational relaxation of the biomolecule itself, however, may be scarce or missing. In this work, we describe in detail the structural changes in DNA undergoing electron transfer between two adjacent nucleobases. We employ an approach based on averaging of tens to hundreds of thousands of nonequilibrium trajectories generated with molecular dynamics simulation, and a reduction of dimensionality suitable for DNA. We show that the conformational response of the DNA proceeds along a single collective coordinate that represents the relative orientation of two consecutive base pairs, namely, a combination of helical parameters shift and tilt. The structure of DNA relaxes on time scales reaching nanoseconds, contributing marginally to the relaxation of energies, which is dominated by the modes of motion of the aqueous solvent. The concept of reaction path averaging (RPA), conveniently exploited in this context, makes it possible to filter out any undesirable noise from the nonequilibrium data, and is applicable to any chemical process in general.Comment: 45 pages, 20 figures, published, added Supplementary informatio

Attosecond spectroscopy of bio-chemically relevant molecules

Understanding the role of the electron dynamics in the photochemistry of bio-chemically relevant molecules is key to getting access to the fundamental physical processes leading to damage, mutation and, more generally, to the alteration of the final biological functions. Sudden ionization of a large molecule has been proven to activate a sub-femtosecond charge flow throughout the molecular backbone, purely guided by electronic coherences, which could ultimately affect the photochemical response of the molecule at later times. We can follow this ultrafast charge flow in real time by exploiting the extreme time resolution provided by attosecond light sources. In this work recent advances in attosecond molecular physics are presented with particular focus on the investigation of bio-relevant molecules

Towards the ionizing radiation induced bond dissociation mechanism in oxygen, water, guanine and DNA fragmentation: a density functional theory simulation

The radiation-induced damages in bio-molecules are ubiquitous processes in radiotherapy and radio-biology, and critical to space projects. In this study, we present a precise quantification of the fragmentation mechanisms of deoxyribonucleic acid (DNA) and the molecules surrounding DNA such as oxygen and water under non-equilibrium conditions using the first-principle calculations based on density functional theory (DFT). Our results reveal the structural stability of DNA bases and backbone that withstand up to a combined threshold of charge and hydrogen abstraction owing to simultaneously direct and indirect ionization processes. We show the hydrogen contents of the molecules significantly control the stability in the presence of radiation. This study provides comprehensive information on the impact of the direct and indirect induced bond dissociations and DNA damage and introduces a systematic methodology for fine-tuning the input parameters necessary for the large-scale Monte Carlo simulations of radio-biological responses and mitigation of detrimental effects of ionizing radiation

Radiation Induced Processes in Biomolecules and Clusters in Controlled Beams

The fundamental nanoscale processes that initiate radiation damage in biological material have not yet been fully elucidated. This represents a significant barrier to developing multidimensional simulations of radiation effects that can lead to advances in radiotherapy and radioprotection. This thesis explores UV- and electron-induced processes in DNA and RNA bases. Pure and hydrated clusters are studied in order to better understand the effects of the chemical environment on the radiation response of these important biomolecules. Although extensive research has been carried out on the relaxation pathways of UV-excited nucleobases, no previous experiments have investigated bond breaking in neutral electronic excited states. This thesis reveals a new fragment ion from uracil (C3H4N2O+) that can be accessed by multi-photon ionization (MPI) but not by electron impact ionization (ElI). This provides the first experimental demonstration that neutral excited state dynamics in a nucleobase can lead to bond breaking in the aromatic ring, as predicted in recent theoretical studies. The specific excited state dynamics have not yet been identified definitively and are the subject of on-going ultrafast pump-probe experiments in collaboration with Townsend and co-workers (Heriot-Watt University). The time-resolved measurements provide new evidence supporting a theoretically predicted relaxation pathway into long-lived triplet states. Dissociative ionization of hydrated nucleobases and uracil-adenine clusters has been studied experimentally for the first time. Evidence for deamination reactions is observed in hydrated adenine complexes. The production of C3H4N2O+ fragments from uracil is strongly suppressed by clustering with water whereas the channel remains open in uracil-adenine complexes. To unravel the specific cluster-mediated dynamics and reactions responsible for these effects, further experiments are required with greater control over the cluster targets. Indeed the range of monomers and cluster configurations in neutral beams currently limits interpretations and direct comparisons with calculations. In response to this challenge, a new experiment has been built that enables radiation effects to be studied on molecules and clusters in Stark-deflected beams (MPI, ElI, and future electron attachment measurements). Early results on nitromethane beams include a demonstration that studying ElI as a function of the Stark deflector voltage can be used to deduce whether certain product ions came from monomers or from clusters