\affiliation[Universit\'{e} de Toulouse (UPS) and CNRS]{Laboratoire de Chimie et Physique Quantiques LCPQ/IRSAMC, Université\'e de Toulouse (UPS) and CNRS, 118 Route de Narbonne, F-31062 Toulouse, France}
\author{Fernand Spiegelman}
\affiliation[Universit\'{e} de Toulouse (UPS) and CNRS]{Laboratoire de Chimie et Physique Quantiques LCPQ/IRSAMC, Université\'e de Toulouse (UPS) and CNRS, 118 Route de Narbonne, F-31062 Toulouse, France}
\author{J\'er\^ome Cuny}
\affiliation[Universit\'{e} de Toulouse (UPS) and CNRS]{Laboratoire de Chimie et Physique Quantiques LCPQ/IRSAMC, Université\'e de Toulouse (UPS) and CNRS, 118 Route de Narbonne, F-31062 Toulouse, France}
{A dynamics collision simulation study on proton localization of uracil protonated water clusters\footnote{A dynamics collision simulation study on proton localization of uracil protonated water clusters}}
A series of dynamics collision simulations between lowest-energy uracil protonated water clusters (H$_2$O)$_{n=3-7, 12}$UH$^+$ and Argon atom were performed with the self-consistent-charge density-functional based tight-binding (SCC-DFTB) method to describe the collision process. From the dynamics collision simulations, the trend of different types of fragments and location of the excess proton were observed. Our initial geometries provided a reasonably uniform distribution of Argon projectiles around each uracil protonated water clusters leading Argon atom can collide at all the possible positions of each cluster. The theoretical simulation data show that the proportion of neutral uracil molecule loss and total fragmentation cross sections are consistent with those in experiment. Additionally, we observed that up to 7 water molecules the clusters had a direct dissociation mechanism after collision \blue{whereas for 12 water molecules …...} Furthermore, the calculation results indicate the excess proton location is highly dependent on the initial isomer as stated in a previous study. \blue{By conducting path-integral MD simulation, we finally observed that nuclear quantum effect XXX.}\blue{We are the first to perform this kind of simulation,} our dynamics collision simulations for predicting the type and amount of fragments and fragmentation cross sections of collision system provide a useful tool.
The nucleobases in DNA and RNA play a very important role in the encoding and expression of genetic information in living systems while water represents the natural medium of many reactions in living organisms. Therefore, it is a significant point to study the interaction between nucleobase molecules and aqueous environment.
The radiation effect on RNA and DNA molecules is still a medical challenge in modern times. The radiation can cause damages on these molecules. Radiation damages are proficiently applied in radiotherapy for cancer treatment. The major drawback in radiotherapy is the unselective damage in both healthy and tumor cells, which has a big side effect. This makes it particularly important to explore the radiation fragments. RNA nucleobase, uracil C$_4$H$_4$N$_2$O$_2$ (U), has attracted scientist’s attention a lot. Protonated uracil UH$^+$ can be generated by radiation damages. Through the study of hydration effects on cytosine, uracil, and thymine pyrimidines by including one and two water molecules explicitly, Schaefer III et al. found that a water molecule is more likely to interact with a charged species than with a neutral one.\cite{Rasmussen2010} However, the study about protonated necleobases in aqueous environment is not so much.
JC MUCH BLABLA
JC Add a sentence to say hydration of molecules can help to do something in real life
Studying hydration of molecules and biomolecules is of paramount important to get insights into their behavior in aqueous medium, in particular their structure, stability and dynamics. To do so, gas phase investigations of molecules play an important role in understanding the intrinsic properties of molecules, which is free from the effects of solvents or other factors. It allows to study the evolution of this behavior as the function of the hydration degree of the molecule and also probe the influence of the protonated state.
Collision experiments in the gas phase is a useful tool that can be applied to provide structural information about molecular species.\cite{Coates2018} For instance, considering U molecule, which has attracted scientist’s attention a lot due to its important role in the encoding and expression of genetic information in living systems, various collision experiments have been conducted. Fragmentation of halogen substituted uracil molecules in the gas phase through collisions experiments have been performed.\cite{Imhoff2007,Abdoul2000,Champeaux2010,Delaunay2014} The theoretical calculations about the charge-transfer processes induced by collision have been also reported.[Doi: 10.1103/PhysRevA.79.012710, DOI: 10.1039/c5cp01475a] Nevertheless, the gas phase study needs to be extended towards more realistic biomolecular systems, to reveal how the intrinsic molecular properties are affected by the surrounding medium when the biomolecules are in a natural environment.[DOI: 10.1002/cphc.201000823, DOI: 10.1088/1742-6596/373/1/012005, DOI: 10.1039/c6cp01940d, DOI: 10.1039/c7cp02233f] (JC, make this part smaller)
It is reported that many collision experiments have been made via threshold collision-induced dissociation (TCID) for the hermodynamic information, electron ionization and fragmentation, binding energies and other properties of biomolecules.[doi: 10.1016/0076-6879(90)93418-K DOI: 10.1021/acs.jpca.7b00635, DOI: 10.1007/s13361-017-1634-y, DOI: 10.1039/c7cp05828d] Fragmentation of isolated protonated uracil has been studied through collision-induced dissociation (CID) with tandem mass sepctrometry,[doi: 10.1016/1044-0305(94)85049-6,
doi:10.1002/jms.3704, doi: 10.1039/C6CP01657J, doi:10.1016/j.cplett.2014.05.026] however, there are few studies concerning the surrounding aqueous environment effect on such collision process in experiment. Some theory studies have been performed about this but those studies have been limited to small water clusters.[Doi: 10.1021/jp806396t] Recently, Zamith’s group in collaboration with our group reported the CID experiment on uracil protonated water clusters (H$_2$O)$_{n=1-15}$UH$^+$ and theoretical study to determine the lowest-energy structures.[doi: 10.1063/1.5044481] In Zamith’s experiment, the collisions only lead to intermolecular bond breaking rather than intramolecular bond breaking in the (H$_2$O)$_{n=1-15}$UH$^+$ clusters. The collisions were performed with H$_2$O, D$_2$O, Ne, and Ar, respectively. The branching ratios of different charged fragments were determined through mass spectra of the collision products. Fragmentation cross section of (H$_2$O)$_{n=1-15}$UH$^+$ clusters were obtained at a collision energy 7.2 eV as a function of the total number molecules in the clusters. The proportion of neutral uracil molecules loss were detected as a function of the number n of water molecules in the (H$_2$O)$_{n=1-15}$UH$^+$ clusters at 7.2 eV center of mass collision energy. From the proportion results of neutral uracil molecules loss, it shows where the excess proton lies after collision. An obvious growth of neutral uracil molecules loss was observed from n=5-6. Those experiment were complemented by theoretical calculations that aim at finding the lowest-energy (H$_2$O)$_{n=1-7}$UH$^+$ clusters. From the structures of lowest-energy isomers, it clearly shows that (i) for small clusters (when n = 1-2), the excess proton is on the uracil; (ii) for n = 3-4, the excess proton is still on the uracil but it has a tendency to be displaced towards adjacent water molecules; (iii) when n is larger than 4, the excess proton is completely transferred to the water clusters. These results are in full agreement with the CID measurements.
However, although the location of the excess proton in lowest-energy isomers is clear, there are still some issues that need to be settled: (i) What’s the main path of the fragmentation mechanisms? (ii) What are the fragments after the collision? (iii) How does the proportion of the fragments change according to the time? (iv) If the proportion of neutral uracil molecules loss only determined by the lowest-energy isomers? With interests in these questions, it pursues us to do an explicit dynamics exploration for these uracil protonated water clusters.
Some studies have already been done about the dynamics collision simulation.[Doi: 10.1063/1.1594717, Doi: 10.1098/rsta.2016.0195, DOI: 10.1039/c8cp03024c] In the present work, we made the dynamics simulation to investigate the collision of (H2O)$_{n=3-7, 12}$UH$^+$ clusters and Ar. Based on the dynamics collision simulations, we analyzed the fragmentation cross section of mixed (H$_2$O)$_{n=3-7, 12}$UH$^+$ clusters according to the total number molecules in the clusters. The branching ratios of different charged fragments were explored of the collision products. The proportion of neutral uracil molecules loss in the mixed (H$_2$O)$_{n=3-7, 12}$UH$^+$ clusters were also investigated. From all the above investigations, the two fragmentation mechanisms after collision, the mixed cluster has an immediately direct dissociation and the mixed cluster has a longer life before completed dissociation, who has the leading position are clear.
\blue{All simulations are performed in the microcanonical ensemble within the Born–Oppenheimer??}
DFTB is approximated from DFT scheme whose efficiency relies on the use of parameterized integrals with a much lower computational cost. The DFTB approach has been particularly well studied and it has already proven its efficiency to describe chemical processes, such as the reactivity[]. In this work, we used the second-order version of DFTB, Self Consistent Charge formulation[biblio] of DFTB, with the mio-set for the Slater-Koster tables of integrals and repulsive interactions. To improve the intermolecular interaction, the class IV/charge model 3 (CM3) charges instead of the original Mulliken charges as well as the empirical terms were used to describe dispersion interactions. For the parameterization of CM3 charges, the bond parameter D$_{OH}$ = 0.129 proposed by Simon and co-workers was applied, \blue{DNH = 0.120 tested by ourselves, (part of this work has been published[])} while all other bond parameter values were set to be 0.000, which corresponds to a Mulliken evaluation of the charges. All the SCC-DFTB calculations in the present work were carried out with the deMonNano code.
All the energy minima for (H2O)n=3-7, have already been obtained in a previous study.[] In this present work, we calculated the lowest-energy isomers of (H$_2$O)$_{12}$UH$^+$ cluster. To obtain them, the same two-step theoretical method with the one used for the calculation of lowest energy isomers of clusters (H$_2$O)$_{n=1-7}$UH$^+$ was applied. Firstly, the potential energy surface (PES) of (H$_2$O)$_{12}$UH$^+$ was roughly explored using the parallel temperature molecular dynamics (PTMD) simulations in combination with SCC-DFTB description of the energies and gradients. In the PTMD algorithm, 40 replicas with temperatures going linearly from 50 to 350 K were carried out. All the trajectories were 4 ns long, and the integration time step was 0.5 fs. A Nosé-Hoover chain of five thermostats with frequencies of 800 cm$^{-1}$ was used to achieve an exploration in the canonical emsemble.To avoid any spurious influence of the initial geometry on the PES exploration, three distinct PTMD simulations were carried out. In the three series, a distinct initial proton location was set: on the uracil in two cases and on the water molecules in another one. In the former cases, the u178 and u138 isomers of UH+ were used as initial geometries, (see Ref. [ ] for the isomer numbering and Fig. 1 for a representation of those isomers) corresponding to the keto-enol and di-keto forms, respectively. 600 geometries per temperature were linearly selected along each PTMD simulation for subsequent geometry optimization leading to 72000 structures optimized at SCC-DFTB level. These structures were sorted in ascending energy order. Secondly, 23 isomers were selected from the 72000 optimized structures at SCC-DFTB level and were optimized at a high accurate MP2/Def2TZVP level, which is a tight criteria for geometry convergence and an ultrafine grid for the numerical integration. From the MP2/Def2TZVP calculation, the lowest energy isomers of cluster (H$_2$O)$_{12}$UH$^+$ were obtained. All MP2 calculations were carried out with the Gaussian 09 package.
Dynamics Collision Simulations
QM/MM method was used to describe the collision process of uracil protonated water cluster (QM) and Argon atom (MM) in the developed deMonNano code. In the dynamics collision calculation, a Fermi distribution (Fermi temperature 2000 K) was applied to determine the molecular orbital occupations. It can avoid the oscillation problems during the search for a self-consistent solution, often taking place when computing DFTB energy for dissociated or close to dissociation systems, and allows to recover the continuity in energy and gradients in the case of level crossing. [doi: 10.1103/PhysRevA.91.043417] In the dynamics collision simulation, at the time of 200 fs, the Argon atom was given a velocity (0.0589 Å·fs$^{-1}$) corresponding to the 7.2 eV center of mass collision energy used in the experiment.[previous paper]. A series of dynamics collision simulation models were generated according to the distance between collision position and the center of the cluster. 600 dynamics collision simulations were performed every 0.5 Å from the center of the cluster for each (H$_2$O)$_{n=3-7, 12}$UH$^+$ at molecular dynamics (MD) bath temperature 25 K. In case missing any collision, we set the biggest distance between collision position and the center of the cluster to be (R + 1) Å rather than the cluster radius R. So totally 600(2R + 3) simulations were calculated. Owing to cluster was set to rotate regularly during the generation of the models, the Ar atom can collide at almost all the possible positions of the cluster. The total simulation time was divided into 600(2R + 3) segments of 15 ps duration for each (H$_2$O)$_{n=3-7, 12}$UH$^+$. After the dynamics collision computation ends of every segment, the geometry of the system was analyzed to detect the possible fragments. A dissociation was defined to arise when the smallest distance between the atoms of two fragments is larger than a given critical distance 5.0 Å.
