Clavulanate is used as an effective drug in combination with β-lactam antibiotics to treat infections of some antibiotic resistant bacteria. Here, we perform combined quantum mechanics/molecular mechanics simulations of several covalent complexes of clavulanate with class A β-lactamases KPC-2 and TEM-1. Simulations of the deacylation reactions identify the decarboxylated trans-enamine complex as being responsible for inhibition. Further, the obtained free energy barriers discriminate clinically relevant inhibition (TEM-1) from less effective inhibition (KPC-2).
The discovery and design of new materials with competitive optical frequency conversion efficiencies can accelerate the development of scalable photonic quantum technologies.
We describe the structure
and properties of [Zn(C6H4N5)N3]n,
a new nonporous three-dimensional high-energy metal–organic
framework (HE-MOF) with enhanced thermal stability. The compound is
synthesized by the hydrothermal method with in situ ligand formation
under controlled pH and characterized using single-crystal X-ray diffraction,
elemental analysis, and Fourier transform infrared. The measured detonation
temperature (Tdet = 345 °C) and heat
of detonation (ΔHdet = −0.380
kcal/g) compare well with commercial explosives and other nitrogen-rich
HE-MOFs. The velocity and pressure of denotation are 5.96 km/s and
9.56 GPa, respectively. Differential scanning calorimetry analysis
shows that the denotation of [Zn(C6H4N5)N3]n occurs via a complex
temperature-dependent mechanism.
Energy transfer (ET) in phycobilisomes, a macrocomplex of phycobiliproteins and linker proteins, is a process that is difficult to understand completely. A model for a rod composed of two hexamers of Phycocyanin and two hexamers of Phycoerythrin was built using an in silico approach and the three-dimensional structures of both phycobiliproteins from Gracilaria chilensis. The model was characterized and showed 125 Å wide and 230 Å high, which agree with the dimensions of a piling of four hexamers as observed in the images of subcomplexes of phycobilisomes obtained by transmission electron microscopy. ET rates between every pair of chromophores in the model were calculated using the F€ orster approach, and the fastest rates were selected to draw preferential ET pathways along the rod. Every path indicates that the ET is funneled toward the chromophores located at Cysteines 82 in Phycoerythrin and 84 in Phycocyanin. The chromophores that face the exterior of the rod are phycoerythrobilins, and they also show a preferential ET toward the chromophores located at the center of the rod. The values calculated, in general, agree with the experimental data reported previously, which validates the use of this experimental approach.
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