Epigenetic modifications are significant processes controlling gene expression. Since their discovery by C. H. Waddington, several multisubject research proceeded and allowed investigation of how biochemical regulations can influence gene transcription. The main epigenetic modification is DNA methylation. This catalytic process of attaching methyl groups to nucleobases (mostly cytosine) is fundamental for the regulation of gene expression and chromatin accessibility. Methylated parts of the genome, which are mostly gene promoters and enhancers, are silenced due to specific biological mechanisms. Scientists postulate that aberrant DNA methylation and other epigenetic modifications can contribute to the development of diverse pathologies such as Alzheimer's disease, epilepsy, Schizophrenia, tumorigenesis, and atherosclerosis. Due to these discoveries, it is important to characterize in detail the mechanism of epigenetic modifications to develop new possible ways of treatment. In this work, we presented complex studies of DNA methylation mechanism including dynamic and energetic analysis of the reaction system. A cluster chemical approach was used to model the active site of enzyme catalyzing methylation - DNMT1 (DNA methyltransferase 1). The created model was subjected to quantum chemical calculations. Geometry optimization was performed with ADF software, providing an energetic characterization of the studied process. Dynamic properties of the enzyme model were described due to molecular dynamics (MD) procedures performed with CP2K software. MD calculations were focused on the observation and description of proton transfer between glutamate acid and cytosine, which is considered the main enzyme-substrate interaction leading to the creation of 5-methylcytosine 5mC (product of the studied reaction) and covalent bonding between enzymes cysteine and nucleobase. This research provides a comprehensive understanding of the DNA methylation mechanism and may contribute to the invention of new drugs and modern ways of treatment.

In this letter, we present the results of the study of the hydrogen bond network of Poly(4-vinylphenol) (PVPh) by using Born-Oppenheimer molecular dynamics. The polymeric structure and IR spectra of PVPh result from the presence of hydrogen bonds between the hydroxyl group. The presented study focuses on the analysis of changes in the network of conjugated hydrogen bonds observed in Poly(4-vinylphenol). The hydroxyl groups form conjugated hydrogen bonds in separate domains. The ab initio molecular dynamics gave us a possibility to understand the stabilization role of the hydrogen bond in the polymer material. Additionally, the quantization of nuclear motion has been performed.

Proton tunneling in the hydrogen-bonded imidazole-imidazolium complex ion has been studied theoretically. Ab initio CASSCF/6-311++G(d,p) calculations concerning geometry optimization and vibrational frequencies have been carried out for equilibrium and transition state structures of the system. Two-dimensional double-well model potentials were constructed on the basis of ab initio results and used to analyze the proton dynamics in the hydrogen bond and the influence of the excitation of low-frequency hydrogen-bond vibrations on the proton tunneling splittings. The energy of tunneling-split vibrational sublevels of the high-frequency tunneling mode have been calculated for its ground and first excited vibrational state for the series of excitations of the coupled low-frequency intramolecular hydrogen-bond modes. The promoting and suppressing effect of the low-frequency modes on the proton splittings was shown in the ground and first excited vibrational state of the tunneling mode. The vibrational sublevels form the two separate semicontinuous bands between which the absorption transitions may occur. This mechanism explains the experimentally observed splitting and doublet-component broadening of the high-frequency N-H stretching infrared (IR) absorption band.

In this work we present the comparison study of Adenine and Thymine crystals based on the hydrogen bond dynamics. The ab initio molecular dynamics have been used as the base for the further studied interactions observed inside crystals. The generated power spectra, as well as the fluctuation of the interaction energies, showed large differences between hydrogen bond networks in the considered crystals. The analysis of intermolecular interactions have been done base on the reactivity descriptors as well frontiers orbitals along trajectories. The main results showed that in adenine crystals the intermolecular interactions have three directions and fluctuate, while in the thymine crystal have only two directions and are weak but stable. These results explain also on the difference between adenine and thymine melting temperature.

In this work, we present the comparison study of guanine and cytosine crystals based on the hydrogen bond (HB) dynamics. The ab initio molecular dynamics gave us a base for detailed analysis. The analysis of the trajectories by power spectrum generation, as well as the fluctuation of the interaction energies, showed large differences between HB networks in the considered crystals. The charge flow is present in the guanine molecule which forms the flat surfaces in the crystals. In the cytosine zigzag structure, the charge flow is blocked. The interaction energy is significantly less stabilizing in the cytosine structure than in the guanine. Finally, the possible influence of charge transfer on the melting temperature has been discussed.

Monoamine oxidase A (MAO A) is a well-known enzyme responsible for the oxidative deamination of several important monoaminergic neurotransmitters. The rate-limiting step of amine decomposition is hydride anion transfer from the substrate α–CH2 group to the N5 atom of the flavin cofactor moiety. In this work, we focus on MAO A-catalyzed benzylamine decomposition in order to elucidate nuclear quantum effects through the calculation of the hydrogen/deuterium (H/D) kinetic isotope effect. The rate-limiting step of the reaction was simulated using a multiscale approach at the empirical valence bond (EVB) level. We applied path integral quantization using the quantum classical path method (QCP) for the substrate benzylamine as well as the MAO cofactor flavin adenine dinucleotide. The calculated H/D kinetic isotope effect of 6.5 ± 1.4 is in reasonable agreement with the available experimental values.

Proton dynamics of hydrogen bonds (HBs) in the and form of Nylon 6 were investigated by Born-Oppenheimer molecular dynamics (BOMD). Our results show differences in the dynamic effects of interchain HB interactions between the form and the form of Nylon 6. Analysis of the time course of the geometrical parameters of HBs along the BOMD simulations has shown that HBs are dynamically favored in the form of Nylon. The quantization of the NH stretching mode enables a detailed discussion of the strengths of HB interactions. Solving the Schrodinger equation for the snapshots of one-dimensional proton potentials, extracted from the ab initio MD, enables the consideration of anharmonicity, thermodynamics, and approximate quantum effects on proton movement. A larger red shift of the NH stretching band was observed in the form compared with the form. Our study shows that HBs are more stabilized in the form than in the form, which is mainly due to the higher number of HBs. The distribution of HBs along the trajectory clearly reveals the preference of the form. The quantization of the NH motion enables the discussion of the differences in the IR spectra between the two forms.

Proton dynamics in a tropolone crystal was studied by 2D quantization of nuclear motions using Born-Oppenheimer molecular dynamics. This study presents the characteristics of the conjugated system of OH stretching vibrations in the tropolone crystal. The MD simulations elucidate the presence of a pseudo-cyclic dimer structure in the crystal phase. The results obtained herein were compared with the IR spectroscopic data for the tropolone crystal. The skeleton and butterfly motions of the seven carbon rings strongly influence the strength of the hydrogen bonds in the cyclic dimers and are extensively discussed in this paper.

Hydrogen bond networks in uracil, 1-methyluracil and 1-methyl-4-thiouracil were studied by ab initio molecular dynamics as well as analysis of the orbital interactions. The power spectra calculated by ab initio molecular dynamics for atoms involved in hydrogen bonds were analyzed. We calculated spectra by using anharmonic approximation based on the autocorrelation function of the atom positions obtained from the Born-Oppenheimer simulations. Our results show the differences between hydrogen bond networks in uracil and its methylated derivatives. The studied methylated derivatives, 1-methyluracil as well as 1-methyl-4-thiouracil, form dimeric structures in the crystal phase, while uracil does not form that kind of structures. The presence of sulfur atom instead oxygen atom reflects weakness of the hydrogen bonds that build dimers.

In this letter we present results of study of weak CH⋯OC hydrogen bonds of crystalline poly-(R)-3-hydroxybutyrate (PHB) by using Born-Oppenheimer molecular dynamics. The polymeric structure and IR spectra of PHB result from the presence of the weak hydrogen bonds. We applied the post-molecular dynamics analysis to consider a CO motion as indirectly involved in the hydrogen bonds. Quantization of the nuclear motion of the oxygens was done to perform detailed analysis of the strength and properties of the CO bands involved in the weak hydrogen bonds. We have also shown the dynamic character of the weak hydrogen bond interactions.

In this study, the proton dynamics of hydrogen bonds for two forms of crystalline aspirin was investigated by the Born-Oppenheimer molecular dynamics (BOMD) method. Analysis of the geometrical parameters of hydrogen bonds using BOMD reveals significant differences in hydrogen bonding between the two crystalline forms of aspirin, Form I and Form II. Analysis of the trajectory for Form I shows spontaneous proton transfer in cyclic dimers, which is absent in Form II. Quantization of the O-H stretching modes allows a detailed discussion on the strength of hydrogen-bonding interactions. The focal point of our study is examination of the hydrogen bond characteristics in the crystal structure and clarification of the influence of hydrogen bonding on the presence of the two crystalline forms of aspirin. In the BOMD method, thermal motions were taken into account. Solving the Schrödinger equation for the snapshots of 2D proton potentials, extracted from MD, gives the best agreement with IR spectra. The character of medium-strong hydrogen bonds in Form I of aspirin was compared with that of weaker hydrogen bonds in aspirin Form II. Two proton minima are present in the potential function for the hydrogen bonds in Form I. The band contours, calculated by using one- and two-dimensional O-H quantization, reflect the differences in the hydrogen bond strengths between the two crystalline forms of aspirin, as well as the strong hydrogen bonding in the cyclic dimers of Form I and the medium-strong hydrogen bonding in Form II.

In this study we present complementary computational and experimental studies of hydrogen bond interaction in crystalline benzoic acid and its deuterated and partially deuterated derivatives. The experimental part of the presented work includes preparation of partially deuterated samples and measurement of attenuated total reflection (ATR)-FTIR spectra. Analysis of the geometrical parameters and time course of dipole moment of crystalline benzoic acid and its deuterated and partially deuterated derivatives by Born-Oppenheimer molecular dynamics (BOMB) enabled us to deeply analyze the IR spectra. Presented simulations based on BOMB gave us opportunity to investigate individual motion and its contribution to the IR spectra. The band contours calculated using Fourier transform of autocorrelation function are in quantitative agreement with the experimental spectra. Characterization of single bands was carried coordinate analysis". The salient point of our study is a comparison of the spectra of the deuterated and partially deuterated crystalline benzoic acid with that of the nondeuterated one. Furthermore, we have applied the principal component analysis for analysis of the number of components in partially deuterated systems. In this study, we reveal that the arrangements of hydrogen and deuterium atoms in partially deuterated samples are random.

Interaction energies, geometry and vibrational frequencies of the gas-phase HF-dimethyl ether complex were obtained using quantum-chemical methods. Equilibrium and vibrationally averaged geometries, harmonic and anharmonic wavenumbers of the complex were calculated using second-order perturbation theory procedures with B3LYP, B2PLYP-D and MP2 methods with 6-311++ G(2df, 2pd) basis set. Quantum-mechanical model describing anharmonic-type vibrational couplings within hydrogen bond was used to explain broadening, fine structure and temperature dependence of the F-H stretching IR absorption bands as effect of hydrogen bond formation. Simulations of the rovibrational structure of the F-H stretching bands were performed for different temperatures. The results were compared with experimental spectra.

We studied proton dynamics of a hydrogen bonds of the crystalline l-ascorbic acid. Our approach was based on the Car-Parrinello molecular dynamics. The focal point of our study was simulation of the infrared spectra of l-ascorbic acid associated with the O-H stretching modes that are very sensitive to the strength of hydrogen bonding. In the l-ascorbic acid there are four kinds of hydrogen bonds. We calculated their spectra by using anharmonic approximation and the time course of the dipole moment function as obtained from the Car-Parrinello simulation. The quantization of the nuclear motion of the protons was made to perform detailed analysis of strength and properties of hydrogen bonds. We presented double minimum proton potentials with small value of barriers for medium-strong hydrogen bonds. We have also shown the difference character of medium-strong hydrogen bonds compared to weaker hydrogen bonds in the l-ascorbic acid.

•Theoretical IR spectra of ice XI were calculated by ab initio CP molecular dynamics.•The assignment of modes was done by analysis of power and polarization spectra.•The results were compared with experimental and other theoretical spectra of ice XI.•Our simulations can be used for investigation of existence of ice XI in space.

Various forms of ice exist within our galaxy. Particularly intriguing type of ice - 'ferroelectric ice' was discovered experimentally and is stable in temperatures below 72 K. This form of ice can generate enormous electric fields and can play an important role in planetary formation. In this letter we present Car-Parrinello simulation of infrared spectra of ferroelectric ice and compare them with spectra of hexagonal ice. Librational region of the spectra can be treated as spectroscopic signature of ice XI and can be of help to identify ferroelectric ice in the Universe. (C) 2014 Elsevier B.V. All rights reserved.