Would the subsitution (due to a mutation) of alanine (hydrophobic amino acid) for serine (a polar and hydrophobic amino acid) have a large or small effect on the structure of a protein?

small effect

Explanation:

Alanine is more hydrophobic whilst serine has a hydroxyl side chain making it polar. The size of these two amino acids is relatively the same.  

The polar hydroxyl group of serine may be well tolerated:

1) If the residue is buried inside the protein core. Hydrophobic interactions are usually buried inside the core of the protein, stabilizing the protein. Introducing a polar residue can destabilize the structure but  because both residues are similar in size, a small cavity forms and may not be disruptive. Water molecules can be introduced in the cavity and compensate.

2) The function can be greatly compromised if the residue is at the active site altering the interactions between nearby residues or substrate.

4

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