Theoretical understanding of the thermodynamics and interactions in transcriptional regulator TtgR–ligand binding
文献信息
The transcriptional regulator TtgR belongs to the TetR family of transcriptional repressors. It depresses the transcription of the TtgABC operon and itself and thus regulates the extrusion of noxious chemicals with efflux pumps in bacterial cells. As the ligand-binding domain of TtgR is rather flexible, it can bind with a number of structurally diverse ligands, such as antibiotics, flavonoids and aromatic solvents. In the current work, we perform equilibrium and nonequilibrium alchemical free energy simulation to predict the binding affinities of a series of ligands targeting the TtgR protein and an agreement between the theoretical prediction and the experimental result is observed. End-point methods MM/PBSA and MM/GBSA are also employed for comparison. We further study the interaction maps and contacts between the protein and the ligand and identify important interactions in the protein–ligand binding cases. The dynamics fluctuation and secondary structures are also investigated. The current work sheds light on atomic and thermodynamic understanding of the TtgR–ligand interactions.
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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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