Theoretical studies on the transport mechanism of 5-fluorouracil through cyclic peptide based nanotubes
Literature Information
Sofie Van Damme, Patrick Bultinck, Venkatesan Subramanian
Cyclic peptide nanotubes (CPNTs) formed by the self-assembly of cyclic peptides (CPs) with an even number of alternate L/D amino acids are typically used in the field of the transport of ions and drug molecules across the lipid bilayer. This study investigates the transport mechanism of the antitumor drug molecule, 5-fluorouracil (5FU), through the CPNT using classical and steered molecular dynamics simulations combined with umbrella sampling. During the transport of 5FU through the CPNT, 5FU is partially desolvated because the lumen of the CPNT is too small to allow for water molecules solvating it. 5FU forms H-bonding interactions with the backbones of the CPNT and at the same time, also forms hydrophobic contacts with the backbone Cα and C atoms of the CPNT. The cooperative breaking of the H-bond and hydrophobic interactions between the CPNT and 5FU increases the pulling force to transport the 5FU from the mid-Cα region to the Cα one. The calculated free energies of binding reveal that the energy barriers for the transport of 5FU are ∼−6.0 and ∼−2.0 kcal mol−1 in the mid-Cα and Cα plane regions, respectively.
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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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