For a large structural protein with 2500 amino acids, compute the percent change represented by a single-residue substitution and then interpret whether such a small percentage change could still be functionally important. Show your calculation and reasoning.

• A. 40% change; the percent change for large proteins is calculated based on hydrophobicity loss, not residue count, making single substitutions highly disruptive in all cases.
• B. 0.04% change; despite the small percent, a substitution at a critical site can significantly impair function by disrupting local interactions and higher-level assembly.
• C. 4% change; such a substitution always causes catastrophic global unfolding because proteins cannot tolerate any alteration in sequence.
• D. 0.004% change; therefore the substitution can never be functionally significant regardless of position.

Answer: (B)