Poly(ethylene glycol) conjugation stabilizes the secondary structure of α-helices by reducing peptide solvent accessible surface area.
نویسندگان
چکیده
We investigate the effect of poly(ethylene glycol) (PEG) side-chain conjugation on the conformational behavior of an α-helix using molecular dynamics simulations in explicit solvents of varying hydrophobicity. Our simulations illustrate an increase in peptide helicity with increasing PEG molecular weight in the range ~400 to 1800 Da. The data with varying PEG contour lengths as well as constant force pulling simulations that allow control over the end-to-end length of PEG indicate a strong inverse correlation between peptide helicity and solvent accessible surface area (SASA). A residue-based mapping analysis reveals that the formation of a protecting PEG shell around peptide helix in water is facilitated by two distinct mechanisms that depend on the solvent environment. First, cationic residues such as lysine interact favorably with PEG due to strong polar interactions with PEG oxygen atoms. Additionally, we find that hydrophobic residues interact strongly with PEG to reduce their SASA in polar solvents by polymer shielding. Our simulations illustrate that these two mechanisms that involve side-chain chemistry and solvent polarity govern the preferred conformation of PEG on the helix surface and thus the stability of peptide secondary structure. These findings elucidate the molecular mechanisms underpinning recent experimental findings on the stability and conformational dynamics of protein-PEG conjugates.
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ورودعنوان ژورنال:
- Biomacromolecules
دوره 14 11 شماره
صفحات -
تاریخ انتشار 2013