PEGylation within a confined hydrophobic cavity of a protein

文献情報

出版日 2019-11-13

DOI 10.1039/C9CP04387J

インパクトファクター 3.676

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要旨

The conjugation of polyethylene glycol (PEG) to proteins, known as PEGylation, has increasingly been employed to expand the efficacy of therapeutic drugs. Recently, research has emphasized the effect of the conjugation site on protein–polymer interactions. In this study, we performed atomistic molecular dynamics (MD) simulations of lysine 116 PEGylated bovine serum albumin (BSA) to illustrate how conjugation near a hydrophobic pocket affects the conjugate's dynamics and observed altered low mode vibrations in the protein. MD simulations were performed for a total of 1.5 μs for each PEG chain molecular mass from 2 to 20 kDa. Analysis of preferential PEG–BSA interactions showed that polymer behavior was also affected as proximity to the attractive protein surface patches promoted interactions in small (2 kDa) PEG chains, while the confined environment of the conjugation site reduced the expected BSA surface coverage when the polymer molecular mass increased to 10 kDa. This thorough analysis of PEG–BSA interactions and polymer dynamics increases the molecular understanding of site-specific PEGylation and enhances the use of protein–polymer conjugates as therapeutics.

掲載誌

Physical Chemistry Chemical Physics

CiteScore: 5.5

自己引用率: 10.3%

年間論文数: 3036

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.