Molecular insights into avibactam mediated class C β-lactamase inhibition: competition between reverse acylation and hydrolysis through desulfation
文献情報
Chandan Kumar Das, Nisanth N. Nair
Avibactam is one of the promising next generation β-lactamase inhibitors due to its exceptional inhibition against wide-spectrum serine β-lactamases. The unusual reversible acylation mechanism has particularly gained interest to explain the inhibition mechanism of avibactam. We explore the mechanism of acylation and deacylation involving avibactam in class-C β-lactamases (CBLs) through hybrid quantum mechanical/molecular mechanical (QM/MM) enhanced sampling molecular dynamics (MD) simulations. Based on these computations, we probe the kinetic stability of the acyl–enzyme complex formed by avibactam and CBLs, thereby gaining molecular level insights into the avibactam-mediated inhibition of CBLs.
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Physical Chemistry Chemical Physics

Physical Chemistry Chemical Physics (PCCP) is an international journal co-owned by 19 physical chemistry and physics societies from around the world. This journal publishes original, cutting-edge research in physical chemistry, chemical physics and biophysical chemistry. To be suitable for publication in PCCP, articles must include significant innovation and/or insight into physical chemistry; this is the most important criterion that reviewers and Editors will judge against when evaluating submissions. The journal has a broad scope and welcomes contributions spanning experiment, theory, computation and data science. Topical coverage includes spectroscopy, dynamics, kinetics, statistical mechanics, thermodynamics, electrochemistry, catalysis, surface science, quantum mechanics, quantum computing and machine learning. Interdisciplinary research areas such as polymers and soft matter, materials, nanoscience, energy, surfaces/interfaces, and biophysical chemistry are welcomed if they demonstrate significant innovation and/or insight into physical chemistry. Joined experimental/theoretical studies are particularly appreciated when complementary and based on up-to-date approaches.










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