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The Role of Hydrophobicity in the Stability and pH-Switchability of (RXDX)4 and Coumarin–(RXDX)4 Conjugate β‑Sheets
journal contribution
posted on 2020-02-21, 21:48 authored by Ryan Weber, Martin McCullaghpH-Switchable,
self-assembling materials are of interest in biological
imaging and sensing applications. Here we propose that combining the
pH-switchability of RXDX (X = Ala, Val, Leu, Ile, Phe) peptides and
the optical properties of coumarin creates an ideal candidate for
these materials. This suggestion is tested with a thorough set of
all-atom molecular dynamics simulations. We first investigate the
dependence of pH-switchabiliy on the identity of the hydrophobic residue,
X, in the bare (RXDX)4 systems. Increasing the hydrophobicity
stabilizes the fiber which, in turn, reduces the pH-switchabilty of
the system. This behavior is found to be somewhat transferable to
systems in which a single hydrophobic residue is replaced with a coumarin
containing amino acid. In this case, conjugates with X = Ala are found
to be unstable at both pHs, while conjugates with X = Val, Leu, Ile,
and Phe are found to form stable β-sheets at least at neutral
pH. The coumarin-(RFDF)4 conjugate is found to have the
largest relative entropy value of 0.884 ± 0.001 between neutral
and acidic coumarin ordering distributions. Thus, we posit that coumarin–(RFDF)4 containing peptide sequences are ideal candidates for pH-sensing
bioelectronic materials.