15. A strong ionic bond is present in R-chains of arginine and aspartic acid. This bond will be weakest if arginine is being replaced by-

    (1) Glutamic Acid
    (2) Lysine
    (3) Histidine
    (4) proline

Effect of Replacement of Arginine on Strength of Ionic Bond in Biomolecules

Comprehension of Ionic Bonds in Amino Acids
Ionic bonds in proteins are important in stabilizing structure and allowing interactions. Ionic bonds are established between positively charged (basic) and negatively charged (acidic) amino acid side chains.

Arginine (R) is a basic amino acid.

Aspartic acid (D) is an acidic amino acid.

Together, they create a strong salt bridge (ionic bond).

How Arginine Replacement Influences Ionic Bond Strength
The ionic bond strength relies on the charge and capacity to create strong electrostatic interactions. Let’s examine potential arginine (R) replacements:

1. Glutamic Acid (E) – Weakest Ionic Bond (✅ Correct Answer)
Glutamic acid (E) is negatively charged, similar to aspartic acid.

Arginine replacement with glutamic acid removes the positive charge, thus inhibiting ionic bond formation.

Result: Ionic bond is lost altogether, hence the weakest substitute.

2. Lysine (K) – Maintains Ionic Bond
Lysine (K) is a basic amino acid, similar to arginine.

It still maintains an ionic bond with aspartic acid, albeit weaker since lysine contains a shorter side chain than arginine.

Result: Ionic bond persists, but less strong.

3. Histidine (H) – Weaker Ionic Bond
Histidine (H) is partially positively charged at physiological pH (~7.4), so its capacity to create a strong ionic bond is pH-dependent.

Outcome: Weaker ionic bond than arginine.

4. Proline (P) – No Ionic Bond
Proline (P) is a neutral amino acid, i.e., it cannot create an ionic bond with aspartic acid.

Proline is not charged like glutamic acid, though, so it does not upset the charge balance as much.

Result: Breakage of ionic bond, but not by charge repulsion.

Correct Answer: (1) Glutamic Acid (E) – Weakest Ionic Bond

Role of Ionic Bonds in Protein Stability

1. Structural Stability
Ionic bonds stabilize protein structure, particularly in enzyme active sites.

2. Protein-Protein Interactions
Numerous cellular processes rely on ionic interactions among proteins.

3. pH Sensitivity
Ionic bonds can be weakened or strengthened by changes in pH, which can impact protein function.

Conclusion
Substitution of arginine with glutamic acid gives the weakest ionic bond since both glutamic acid and aspartic acid are negatively charged, which removes electrostatic attraction. These substitutions are useful in protein engineering, drug design, and biochemistry studies.