Cefiderocol-Based Regimen for Acinetobacter NDM-1 Outbreak.

Variable outcomes have been reported with cefiderocol in infections due to carbapenem-resistant (CRAB). Nonetheless, it may be the only option for metallo-beta-lactamase-producing strains. We describe an outbreak of NDM-CRAB infections treated with cefiderocol.

Combining the Fragment Molecular Orbital and GRID Approaches for the Prediction of Ligand-Metalloenzyme Binding Affinity: The Case Study of hCA II Inhibitors.

Polarization and charge-transfer interactions play an important role in ligand-receptor complexes containing metals, and only quantum mechanics methods can adequately describe their contribution to the binding energy. In this work, we selected a set of benzenesulfonamide ligands of human Carbonic Anhydrase II (hCA II)-an important druggable target containing a Zn ion in the active site-as a case study to predict the binding free energy in metalloprotein-ligand complexes and designed specialized computational methods that combine the ab initio fragment molecular orbital (FMO) method and GRID approach. To reproduce the experimental binding free energy in these systems, we adopted a machine-learning approach, here named formula generator (FG), considering different FMO energy terms, the hydrophobic interaction energy (computed by GRID) and logP.

Improving the accuracy of the FMO binding affinity prediction of ligand-receptor complexes containing metals.

Polarization and charge transfer strongly characterize the ligand-receptor interaction when metal atoms are present, as for the Au(I)-biscarbene/DNA G-quadruplex complexes. In a previous work (J Comput Aided Mol Des2022, 36, 851-866) we used the ab initio FMO2 method at the RI-MP2/6-31G* level of theory with the PCM [1] solvation approach to calculate the binding energy (ΔE) of two Au(I)-biscarbene derivatives, [Au(9-methylcaffein-8-ylidene)] and [Au(1,3-dimethylbenzimidazole-2-ylidene)], able to interact with DNA G-quadruplex motif. We found that ΔE and ligand-receptor pair interaction energies (E) show very large negative values making the direct comparison with experimental data difficult and related this issue to the overestimation of the embedded charge transfer energy between fragments containing metal atoms.

IRMPD spectroscopy and quantum-chemical simulations of the reaction products of cisplatin with the dipeptide CysGly.

The inorganic antineoplastic drug cisplatin was made to react in solution with the dipeptide cysteinylglycine (CysGly), chosen as a functional model of glutathione, and the reaction products were analyzed using electrospray ionization mass spectrometry (ESI-MS). Selected complexes, i.e.

The FMO2 analysis of the ligand-receptor binding energy: the Biscarbene-Gold(I)/DNA G-Quadruplex case study.

In this work, the ab initio fragment molecular orbital (FMO) method was applied to calculate and analyze the binding energy of two biscarbene-Au(I) derivatives, [Au(9-methylcaffein-8-ylidene)] and [Au(1,3-dimethylbenzimidazol-2-ylidene)], to the DNA G-Quadruplex structure. The FMO2 binding energy considers the ligand-receptor complex as well as the isolated forms of energy-minimum state of ligand and receptor, providing a better description of ligand-receptor affinity compared with simple pair interaction energies (PIE). Our results highlight important features of the binding process of biscarbene-Au(I) derivatives to DNA G-Quadruplex, indicating that the total deformation-polarization energy and desolvation penalty of the ligands are the main terms destabilizing the binding.