Search

Alligator sinensis cathelicidins (As-CATHs) are antimicrobial peptides extracted from alligators that enable alligators to cope with diseases caused by bacterial infections. This study assessed the damaging effects of sequence-truncated and residue-substituted variants of As-CATH4, AS4-1, AS4-5, and AS4-9 (with decreasing charges but increasing hydrophobicity) on the membranes of Gram-negative bacteria at the molecular level by using coarse-grained molecular dynamics simulations. The simulations predicted that all the variants disrupt the structures of the inner membrane of Gram-negative bacteria, with AS4-9 having the highest antibacterial activity that is able to squeeze the membrane and extract lipids from the membrane. However, none of them can disrupt the structure of asymmetric outer membrane of Gram-negative bacteria, which is composed of lipopolysaccharides in the outer leaflet and phospholipids in the inner leaflet. Nonetheless, the adsorption of AS4-9 induces lipid scrambling in the membrane by lowering the free energy of a phospholipid flipping from the inner leaflet up to the outer leaflet. Upon binding onto the lipid-scrambled outer membrane, AS4-9s are predicted to squeeze and extract phospholipids from the membrane, AS4-5s have a weak pull-out effect, and AS4-1s mainly stay free in water without any lipid-extracting function. These findings provide inspiration for the development of potent therapeutic agents targeting bacteria. [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]

Temporins are a family of antimicrobial peptides (AMPs) isolated from frog skin, which are very short, weakly charged, and highly hydrophobic. They execute bactericidal activities in different ways from many other AMPs. This work investigated morphological changes of planar bilayer membranes composed of mixed zwitterionic and anionic phospholipids induced by temporin B and L (TB and TL) using all-atom and coarse-grained molecular dynamics simulations. We found that TB and TL fold to α-helices at the membrane surface and penetrate shallowly into the bilayer. These short AMPs have low propensity to induce membrane pore formation but possess high ability to extract lipids out. At relatively high peptide concentrations, the strong hydrophobicity of TB and TL promotes them to aggregate into clusters on the membrane surface. These aggregates attract a large amount of lipids out of the membrane to release compression induced by other dispersed peptides binding to the membrane. The extruded lipids mix evenly with the peptides in the cluster and form tubule-like protrusions. Certain water molecules follow the movement of lipids, which not only fill the cavities of the protrusion but also assist in maintaining the tubular structures. In contrast, the peptide-free leaflet remains intact. The present results unravel distinctive antimicrobial mechanisms of temporins disturbing membranes. [ABSTRACT FROM AUTHOR]

• CO 2 reacts with methyl groups to both promote and inhibit combustion. • CO 2 is weakly oxidizing and can participate in chemical reactions. • CO 2 also reacts with formaldehyde, ethylene and vinyl. The study aims to examine the impact of CO 2 concentration gradient on the ignition and combustion of a diesel surrogate fuel composed of 70% C 7 H 16 and 30% C 7 H 8. The investigation focuses on the weak oxidation of CO 2 through its reaction with methyl groups (CH, CH 2 , and CH 3 radicals). Firstly, the molecular bond-breaking recombination process between CO 2 and methyl groups is calculated using Born-Oppenheimer molecular dynamics with the UB3LYP/6–311++g (d, p) level of theory. Subsequently, the electronic distribution and competition of the molecule surface are analyzed through various wave function analyses to identify the reactive sites. Secondly, the precise potential energy surface and reaction rate are calculated based on the acquired reaction process information. This calculation employs the B2PLYP/def2-TZVP level of theory and transition state theory. Finally, extensive molecular dynamics simulations of CO 2 and methyl groups are conducted using reaction force fields. These simulations provide insights into the temperature-energy variation within the system and the resulting chemical reaction network. The optimized combustion mechanism for the binary fuel is derived, focusing exclusively on the influences of CO 2 and O 2 while excluding those of N 2 and other extraneous gases. The results demonstrate exothermic reactions of CO 2 with CH and CH 2 radicals at 850 K, yielding ΔG values of −238.91 kJ/mol and −209.96 kJ/mol, respectively. Conversely, CO 2 reacts with CH 3 radicals in heat-absorbing reactions at 850 K, resulting in a ΔG of 491.73 kJ/mol. Additionally, the chemical impact of CO 2 exhibits both promotional and inhibitory effects on combustion. The CO 2 molecule exhibits weak oxidation properties due to the presence of active sites on its surface characterized by minimal values of electrostatic potential (-50.17 kJ/mol) and average local ionization energy (61.92 kJ/mol) at the O-atomic end. The molecular dynamics process involving the methyl groups and CO 2 system exhibits a heat absorption phenomenon. This behavior can be attributed to the participation of CO 2 not only in the reactions with methyl groups but also with formaldehyde and ethylene, among others. [ABSTRACT FROM AUTHOR]

• The formation of the soot nanoparticle undergoes four processes. • Initial pyrolysis provides the reactant source for the formation of soot precursor. • The soot particle undergoes the surface growth and the morphological rearrangement. • Higher temperature can accelerate the formation of soot particle. The chemical-kinetic mechanism of soot formation for the n -decane pyrolysis was comprehensively investigated from theoretical perspective. We found the formation of carbonaceous nanoparticle with a multi-layer closed cylindrical structure needs four processes including initial rings formation, PAH growth, particle nucleation via coalescence of PAH and particle growth by coagulation or surface reactions. The mechanisms of HACA, CAHM and CHRCR play crucial roles in the processes of the formation and growth of PAH molecules. In addition, the temperature effect was discussed and found the higher temperature can accelerate the formation of soot particle, which is in agreement with the experiment findings. [ABSTRACT FROM AUTHOR]