Question

In which direction do you think the pK_a of aspartate would shift when it is buried in the hydrophobic interior of a protein, and does not form an ion pair with a positively charged group? Explain in 1-2 sentences.

Answer 1

• In general, the pKa values of internal groups in proteins are shifted relative to the normal pKa values in water. This coupling between pKa and protein conformation is responsible for the pH dependence of thermodynamic stability
• By analyzing the amount and distribution of buried charged surface and charges in proteins over a broad range of protein sizes, we show that buried charge is much more common than is generally believed. We also show that the amount of buried charge rises with protein size in a manner which differs from other types of surfaces, especially aromatic and polar uncharged surfaces.
• aspartate (Asp) and glutamate (Glu) both carrying negative charge at neutral pH. On the other hand, polarity is not always straightforward to assign.

  the results on a set of protein‐based polymers (model proteins) that exhibit hydrophobic folding and assembly transitions, and that have been designed for the purpose of achieving large hydrophobic‐induced pKa shifts by selectively replacing Val residues by Phe residues.