Computational search for drug repurposing to identify potential inhibitors against SARS-COV-2 using Molecular Docking, QTAIM and IQA methods in viral Spike protein - Human ACE2 interface.

With the advancement of the Covid-19 pandemic, this work aims to find molecules that can inhibit the attraction between the Spike proteins of the SARS-COV-2 virus and human ACE2. The results of molecular docking positioned four molecules at the interaction site Tyr-491(Spike)-Glu-37(ACE2) and one at the site Gly-488(Spike)-Lys-353(ACE2). The QTAIM and IQA data showed that the 1629 molecule had a significant inhibitory effect on the Gly488-Ly353 site, decreasing the Laplacian of the electronic density of the BCP O4-N10. The molecule 2542 showed an inhibitory effect in two regions of interaction of the Tyr491-Glu37 site, acting on the BCPs H30-H33 and O8-H31 while the ligand 2600, in conformation 26, presented a similar effect only on the BCP O8-H31 of that same interactive site. Thus, the data suggest laboratory tests of a combination of molecules that can act at two sites of interaction simultaneously, using the combination of 1629/2542 and 1629/2600 ligands.

Towards a continuous population model for natural language vowel shift.

The Great English Vowel Shift of 16th-19th centuries and the current Northern Cities Vowel Shift are two examples of collective language processes characterized by regular phonetic changes, that is, gradual changes in vowel pronunciation over time. Here we develop a structured population approach to modeling such regular changes in the vowel systems of natural languages, taking into account learning patterns and effects such as social trends. We treat vowel pronunciation as a continuous variable in vowel space and allow for a continuous dependence of vowel pronunciation in time and age of the speaker. The theory of mixtures with continuous diversity provides a framework for the model, which extends the McKendrick-von Foerster equation to populations with age and phonetic structures. We develop the general balance equations for such populations and propose explicit expressions for the factors that impact the evolution of the vowel pronunciation distribution. For illustration, we present two examples of numerical simulations. In the first one we study a stationary solution corresponding to a state of phonetic equilibrium, in which speakers of all ages share a similar phonetic profile. We characterize the variance of the phonetic distribution in terms of a parameter measuring a ratio of phonetic attraction to dispersion. In the second example we show how vowel shift occurs upon starting with an initial condition consisting of a majority pronunciation that is affected by an immigrant minority with a different vowel pronunciation distribution. The approach developed here for vowel systems may be applied also to other learning situations and other time-dependent processes of cognition in self-interacting populations, like opinions or perceptions.

How accessible is atomic charge information from infrared intensities? A QTAIM/CCFDF interpretation.

Infrared fundamental intensities calculated by the quantum theory of atoms in molecules/charge-charge flux-dipole flux (QTAIM/CCFDF) method have been partitioned into charge, charge flux, and dipole flux contributions as well as their charge-charge flux, charge-dipole flux, and charge flux-dipole flux interaction contributions. The interaction contributions can be positive or negative and do not depend on molecular orientations in coordinate systems or normal coordinate phase definitions, as do CCFDF dipole moment derivative contributions. If interactions are positive, their corresponding dipole moment derivative contributions have the same polarity reinforcing the total intensity estimates whereas negative contributions indicate opposite polarities and lower CCFDF intensities. Intensity partitioning is carried out for the normal coordinates of acetylene, ethylene, ethane, all the chlorofluoromethanes, the X(2)CY (X = F, Cl; Y = O, S) molecules, the difluoro- and dichloroethylenes and BF(3). QTAIM/CCFDF calculated intensities with optimized quantum levels agree within 11.3 km mol(-1) of the experimental values. The CH stretching and in-plane bending vibrations are characterized by significant charge flux, dipole flux, and charge flux-dipole flux interaction contributions with the negative interaction tending to cancel the individual contributions resulting in vary small intensity values. CF stretching and bending vibrations have large charge, charge-charge flux, and charge-dipole flux contributions for which the two interaction contributions tend to cancel one another. The experimental CF stretching intensities can be estimated to within 31.7 km mol(-1) or 16.3% by a sum of these three contributions. However, the charge contribution alone is not successful at quantitatively estimating these CF intensities. Although the CCl stretching vibrations have significant charge-charge flux and charge-dipole flux contributions, like those of the CF stretches, both of these interaction contributions have opposite signs for these two types of vibrations.

Physical analysis of an Antarctic ice core-towards an integration of micro- and macrodynamics of polar ice.

Microstructures from deep ice cores reflect the dynamic conditions of the drill location as well as the thermodynamic history of the drill site and catchment area in great detail. Ice core parameters (crystal lattice-preferred orientation (LPO), grain size, grain shape), mesostructures (visual stratigraphy) as well as borehole deformation were measured in a deep ice core drilled at Kohnen Station, Dronning Maud Land (DML), Antarctica. These observations are used to characterize the local dynamic setting and its rheological as well as microstructural effects at the EDML ice core drilling site (European Project for Ice Coring in Antarctica in DML). The results suggest a division of the core into five distinct sections, interpreted as the effects of changing deformation boundary conditions from triaxial deformation with horizontal extension to bedrock-parallel shear. Region 1 (uppermost approx. 450 m depth) with still small macroscopic strain is dominated by compression of bubbles and strong strain and recrystallization localization. Region 2 (approx. 450-1700 m depth) shows a girdle-type LPO with the girdle plane being perpendicular to grain elongations, which indicates triaxial deformation with dominating horizontal extension. In this region (approx. 1000 m depth), the first subtle traces of shear deformation are observed in the shape-preferred orientation (SPO) by inclination of the grain elongation. Region 3 (approx. 1700-2030 m depth) represents a transitional regime between triaxial deformation and dominance of shear, which becomes apparent in the progression of the girdle to a single maximum LPO and increasing obliqueness of grain elongations. The fully developed single maximum LPO in region 4 (approx. 2030-2385 m depth) is an indicator of shear dominance. Region 5 (below approx. 2385 m depth) is marked by signs of strong shear, such as strong SPO values of grain elongation and strong kink folding of visual layers. The details of structural observations are compared with results from a numerical ice sheet model (PISM, isotropic) for comparison of strain rate trends predicted from the large-scale geometry of the ice sheet and borehole logging data. This comparison confirms the segmentation into these depth regions and in turn provides a wider view of the ice sheet.This article is part of the themed issue 'Microdynamics of ice'.

Study on molecular structure, spectroscopic properties (FTIR and UV-Vis), NBO, QTAIM, HOMO-LUMO energies and docking studies of 5-fluorouracil, a substance used to treat cancer.

Cancer cells can expand to other parts of body through blood system and nodes from a mechanism known as metastasis. Due to the large annual growth of cancer cases, various biological targets have been studied and related to this disorder. A very interesting target related to cancer is human epidermal growth factor receptor 2 (HER2). In this study, we analyzed the main intermolecular interactions between a drug used in the cancer treatment (5-fluorouracil) and HER2. Molecular modeling methods were also employed to assess the molecular structure, spectroscopic properties (FTIR and UV-Vis), NBO, QTAIM and HOMO-LUMO energies of 5-FU. From the docking simulations it was possible to analyze the interactions that occur between some residues in the binding site of HER2 and 5-FU. To validate the choice of basis set that was used in the NBO and QTAIM analyses, theoretical calculations were performed to obtain FT-IR and UV/Vis spectra, and the theoretical results are consistent with the experimental data, showing that the basis set chosen is suitable. For the maximum λ from the theoretical calculation (254.89nm) of UV/Vis, the electronic transition from HOMO to LUMO occurs at 4.89eV. From NBO analyses, we observed interactions between Asp863 and 5-FU, i.e. the orbitals with high transfer of electrons are LP O15 (donor NBO) and BD* (π) N1-H10 (acceptor NBO), being that the value of this interaction is 7.72kcal/mol. Results from QTAIM indicate one main intermolecular H bond, which is necessary to stabilize the complex formed between the ligands and the biological target. Therefore, this study allowed a careful evaluation on the main structural, spectroscopic and electronic properties involved in the interaction between 5-FU and HER2, an important biological complex related to the cancer treatment.

QTAIM charge-charge flux-dipole flux models for the infrared fundamental intensities of difluoro- and dichloroethylenes.

A quantum theory of atoms in molecules (QTAIM) charge-charge flux-dipole flux (CCFDF) decomposition of the MP2/6-311++G(3d,3p) level molecular dipole moment derivatives is reported for the cis-, trans-, and 1,1-difluoroethylenes and the cis- and trans-dichloroethylenes. Although the dipole moment derivatives and infrared fundamental intensities calculated at the MP2 level are overestimated for high-intensity bands corresponding to CF and CC stretching vibrations, the overall agreement is good with a root-mean-square (rms) error of 19.6 km mol-1 for intensities ranging from 0 to 217.7 km mol-1. The intensities calculated from the QTAIM/CCFDF model parameters are in excellent agreement with those calculated directly by the MP2/6-311++G(3d,3p) approach with only a 1.8 km mol-1 rms error. A high negative correlation (r=-0.91) is found between the charge flux and dipole flux contributions to the dipole moment derivatives. Characteristic values of charge, charge flux, and dipole flux contributions are found for CF, CCl, and CH stretching derivatives. The CH stretching derivatives provide especially interesting results with very high charge flux and dipole flux contributions with opposite signs. The charge, charge flux, and dipole flux contributions are found to be transferable from the cis to the trans isomers providing accurate predictions of the theoretical trans intensities with rms errors of 8.6 km mol-1 for trans-difluoroethylene and 5.9 km mol-1 for trans-dichloroethylene.

Quantum theory of atoms in molecules charge-charge flux-dipole flux models for the infrared intensities of X(2)CY (X = H, F, Cl; Y = O, S) molecules.

The molecular dipole moments, their derivatives, and the fundamental IR intensities of the X2CY (X = H, F, Cl; Y = O, S) molecules are determined from QTAIM atomic charges and dipoles and their fluxes at the MP2/6-311++G(3d,3p) level. Root-mean-square errors of +/-0.03 D and +/-1.4 km mol(-1) are found for the molecular dipole moments and fundamental IR intensities calculated using quantum theory of atoms in molecules (QTAIM) parameters when compared with those obtained directly from the MP2/6-311++G(3d,3p) calculations and +/-0.05 D and 51.2 km mol(-1) when compared with the experimental values. Charge (C), charge flux (CF), and dipole flux (DF) contributions are reported for all the normal vibrations of these molecules. A large negative correlation coefficient of -0.83 is calculated between the charge flux and dipole flux contributions and indicates that electronic charge transfer from one side of the molecule to the other during vibrations is accompanied by a relaxation effect with electron density polarization in the opposite direction. The characteristic substituent effect that has been observed for experimental infrared intensity parameters and core electron ionization energies has been applied to the CCFDF/QTAIM parameters of F2CO, Cl2CO, F2CS, and Cl2CS. The individual atomic charge, atomic charge flux, and atomic dipole flux contributions are seen to obey the characteristic substituent effect equation just as accurately as the total dipole moment derivative. The CH, CF, and CCl stretching normal modes of these molecules are shown to have characteristic sets of charge, charge flux, and dipole flux contributions.