Protein flexibility reduces solvent-mediated friction barriers of ligand binding to a hydrophobic surface patch

Literature Information

Publication Date 2021-02-25
DOI 10.1039/D1CP00181G
Impact Factor 3.676
Authors

Christopher Päslack, Lars V. Schäfer, Matthias Heyden


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Abstract

Solvent fluctuations have been explored in detail for idealized and rigid hydrophobic model systems, but so far it has remained unclear how internal protein motions and their coupling to the surrounding solvent affect the dynamics of ligand binding to biomolecular surfaces. Here, molecular dynamics simulations were used to elucidate the solvent-mediated binding of a model ligand to the hydrophobic surface patch of ubiquitin. The ligand's friction profiles reveal pronounced long-time correlations and enhanced friction in the vicinity of the protein, similar to idealized hydrophobic surfaces. Interestingly, these effects are shaped by internal protein motions. Protein flexibility modulates water density fluctuations near the hydrophobic surface patch and smooths out the friction profile of ligand binding.

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Physical Chemistry Chemical Physics

Physical Chemistry Chemical Physics
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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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