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Amidst the unprecedented 2019 coronavirus outbreak and the substantial loss of lives due to the scarcity of information about the virus and lack of viable drugs, understanding the impact of the nCoV Main Protease (Mpro) on the endocrine system has emerged as a critical topic to pursue. This study explores the potential interactions between four key hormones (cortisol, cortisone, estradiol, and estrone) and the Mpro of nCoV using various in‐silico methodologies. Density Functional Theory (DFT) calculations scrutinized the electron density delocalization of these hormones. Through molecular docking, the molecular‐level binding of Mpro of nCoV with these hormones was studied, revealing cortisol as the hormone exhibiting the most promising binding affinity (−100.05 kcal/mol). Furthermore, molecular dynamics (MD) simulations, emulating human body conditions at distinct temperatures, were employed to study the implications of these interactions. The study analysed the various trajectories such as root mean square deviation (RMSD), root mean square fluctuations (RMSF), radius of gyration (Rg), and H‐bond trajectories to understand the potential impact on biological systems. The findings demonstrate the binding potential of the Mpro of nCoV with these hormones, raising plausible concerns regarding consequential physiological changes within the human body. [ABSTRACT FROM AUTHOR]

Three α-dicarbonyl compounds, methylglyoxal (MGO), diacetyl (DA) and glyoxal (GO) were common highly reactive glycosylation intermediates that can cause damage to biological macromolecules (e. g. DNA) in the body. The interaction properties of MGO, DA and GO with calf thymus DNA (ctDNA) were determined by multispectral methods combined with computer simulation techniques. Analysis of UV spectra indicated that MGO, DA and GO binding to ctDNA spontaneously were mainly driven by van der Waals forces and hydrogen bonding, and the energy distribution in molecular dynamics simulations supported this conclusion. The binding constants of MGO, DA and GO with ctDNA at 25 ℃ were close to those of classical groove-binders, with corresponding values of 2.99×10³, 1.96×10³ and 1. 05×10³ L·mol-1, respectively. NaCl, single and double-stranded DNA, thermal denaturation, viscosity and CD spectroscopy experiments demonstrated that MGO, DA and GO were all bound to ctDNA via groove binding. Molecular docking visualization showed that MGO, DA and GO were bound in the AT-rich minor groove region of DNA, with DT7 and DA18 being the active sites of binding. Molecular dynamics simulations of the MGO-ctDNA complex had higher root mean square deviation, radius of gyration, and root mean square fluctuation values than free DNA, indicating that the binding of MGO loosened and tended to destabilise parts of the DNA structure. Gel electrophoresis experiments showed that MGO, DA and GO could damage plasmid DNA in the presence of lysine and Cu2+, and MGO and GO even completely disrupted the superhelical morphology of DNA. [ABSTRACT FROM AUTHOR]

HIV-1 maturation is the final step in the retroviral lifecycle that is regulated by the proteolytic cleavage of the Gag precursor protein. As a first-in-class HIV-1 maturation inhibitor (MI), bevirimat blocks virion maturation by disrupting capsid-spacer peptide 1 (CA-SP1) cleavage, which acts as the target of MIs. Previous alterations of beesioside I (1) produced (20S,24S)-15ꞵ,16ꞵ-diacetoxy-18,24; 20,24-diepoxy-9,19-cyclolanostane-3ꞵ,25-diol 3-O-3′,3′-dimethylsuccinate (3, DSC), showing similar anti-HIV potency compared to bevirimat. To ascertain the binding modes of this derivative, further modification of compound 1 was conducted. Three-dimensional quantitative structure–activity relationship (3D-QSAR) analysis combined with docking simulations and molecular dynamics (MD) were conducted. Five new derivatives were synthesized, among which compound 3b showed significant activity against HIV-1NL4-3 with an EC50 value of 0.28 µM. The developed 3D-QSAR model resulted in great predictive ability with training set (r2 = 0.99, q2 = 0.55). Molecular docking studies were complementary to the 3D-QSAR analysis, showing that DSC was differently bound to CA-SP1 with higher affinity than that of bevirimat. MD studies revealed that the complex of the ligand and the protein was stable, with root mean square deviation (RMSD) values <2.5 Å. The above results provided valuable insights into the potential of DSC as a prototype to develop new antiviral agents. [ABSTRACT FROM AUTHOR]

• Water desalination laws and related mechanisms of HCM were investigated by the MD simulations. • Microscopic mechanism of raw water temperature affects HCM membrane flux was clarified. • Diffusion form of free-state water molecules in the membrane micropores of HCM was ascertained. With LAMMPS software, the non-equilibrium molecular dynamics (NEMD) simulations study was conducted for the membrane distillation process with the hydrophobic α-Al 2 O 3 ceramic membrane (HCM). It could further help to explain the macroscopic laws and phenomena that appeared in the membrane distillation tests with HCM. In this study, the average temperature (T r) of raw water and the negative pressure (P con) on the cold side of HCM were taken as the investigation variables to research the microscopic water desalination performance of HCM, transport/diffusion properties of water molecules, and related mechanisms. The results showed that the root means square displacement (MSD) of water molecules on the cold side of HCM positively changed with time by the linear trend. The height of the transmembrane energy barrier mainly depends on the atomic structure of the HCM. The diffusion type of free-state water molecules in the membrane micropores of HCM was the main ballistic-transport-like accompanied by rebound-jump. The influence level of T r on the number of water molecules in the cold side of HCM was much greater than that of P con under the dynamic equilibrium state. The essential reason T r determined the HCM molecular flux was that it changed the hydrogen bond lifetime in the microporous membrane of HCM. [ABSTRACT FROM AUTHOR]

Molecular dynamics simulations and 2D-NOESY spectroscopy were applied to study the conformations and hydrogen-bonding interactions of ACE-inhibitory tripeptide Gly-Glu-Phe (GEF) in aqueous and DMSO solutions. The properties of GEF in simulations were characterized by intramolecular distance, root-mean-square deviation, solvent-accessible surface, and radius of gyration. Interestingly, the GEF molecule showed different behavior in different solvents. In aqueous solution, the GEF was highly flexible, and it could quickly convert from extended state to folded state. However, in DMSO solution, the extended conformations were hardly observed. The GEF molecule preferred extended state in aqueous compared to DMSO solution, which was confirmed by 2D-NOESY. [ABSTRACT FROM AUTHOR]

Cysteine dioxygenase (CDO) regulates the concentration of l -cysteine substrate by its oxidation in the body to prevent different diseases, including neurodegenerative and autoimmune diseases. CDO catalyzes the oxidation of thiol group of l -cysteine to l -cysteine sulfinic acid using molecular oxygen. In this study, molecular dynamics simulations were applied to ligand-free CDO, cysteine-bound CDO, and oxygen-bound CDO-cysteine complex which were primarily subjected to the evaluation of their structural and dynamical properties. The simulation data provided significant information not only on the conformational changes of the enzyme after its ligation but also on the co-ligation by sequential binding of l -cysteine and molecular oxygen. It was found that the ligation and co-ligation perturbed the active site region as well as the overall protein dynamics which were analyzed in terms of root mean square deviation, root mean square fluctuation and dynamic cross correlation matrices as well as principal component analysis. Furthermore, oxygen transport pathways were successfully explored by taking various tunnel clusters into account and one of those clusters was given preference based on the throughput value. The bottleneck formed by different amino acid residues was examined to figure out their role in the oxygenation process of the enzyme. The residues forming the tunnel's bottleneck and their dynamics mediated by water molecules were further investigated using radial distribution functions which gave insights into the hydration behavior of these residues. The findings based on the hydration behavior in turn served to explore the water-mediated dynamics of these residues in the modulation of the pathway, including tunnel gating for the oxygen entry and diffusion to the active site, which is essential for the CDO's catalytic function. Molecular dynamics simulations were applied to cysteine dioxygenase and its complexes to investigate their structural and dynamical properties as well as to explore the oxygen tunnels involved in the oxygenation process of the enzyme. [Display omitted] • Evaluation of the structural and dynamical properties. • Exploration of the oxygen transport tunnel. • Evaluation of the hydration behavior of the tunnel residues involved in the oxygen of CDO enzyme. [ABSTRACT FROM AUTHOR]

Abstract: Riboswitches are RNA-based genetic control elements that function via a conformational transition mechanism when a specific target molecule binds to its binding pocket. To facilitate an atomic detail interpretation of experimental investigations on the role of the adenine ligand on the conformational properties and kinetics of folding of the add adenine riboswitch, we performed molecular dynamics simulations in both the presence and the absence of the ligand. In the absence of ligand, structural deviations were observed in the J23 junction and the P1 stem. Destabilization of the P1 stem in the absence of ligand involves the loss of direct stabilizing interactions with the ligand, with additional contributions from the J23 junction region. The J23 junction of the riboswitch is found to be more flexible, and the tertiary contacts among the junction regions are altered in the absence of the adenine ligand; results suggest that the adenine ligand associates and dissociates from the riboswitch in the vicinity of J23. Good agreement was obtained with the experimental data with the results indicating dynamic behavior of the adenine ligand on the nanosecond time scale to be associated with the dynamic behavior of hydrogen bonding with the riboswitch. Results also predict that direct interactions of the adenine ligand with U74 of the riboswitch are not essential for stable binding although it is crucial for its recognition. The possibility of methodological artifacts and force-field inaccuracies impacting the present observations was checked by additional molecular dynamics simulations in the presence of 2,6-diaminopurine and in the crystal environment. [Copyright &y& Elsevier]