45. If the backbone -NH2 group in amino acids are modified to -NH(CH3) group, how
will the allowed regions in Ramachandran map of the modified protein change?
A. Allowed region remain unchanged.
B. Allowed regions shrink.
C. Allowed regions expand.
D. It depends on the specific amino acid side chains.
The correct answer is B. Allowed regions shrink. Replacing the backbone -NH2 group with -NH(CH3) introduces steric bulk from the methyl group, restricting phi (φ) and psi (ψ) dihedral angles in the Ramachandran plot. This modification limits access to certain conformations, particularly excluding α-helical regions.
Backbone Modification Mechanism
N-methylation of the amide nitrogen adds a methyl substituent, increasing steric hindrance around the peptide bond. Standard Ramachandran plots for alanine-like dipeptides show allowed regions based on van der Waals clashes, but N-methylation further constrains the backbone by disfavoring negative φ angles typical of helices (φ ≈ -60°). Simulated Ramachandran plots confirm this shrinks the accessible φ/ψ space for both the modified residue and adjacent ones, favoring extended or turn-like conformations instead.
Option Analysis
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A. Allowed region remain unchanged: Incorrect, as the added methyl group creates new steric clashes not present in unmodified amides, altering φ/ψ distributions beyond standard side-chain effects like glycine’s expanded plot.
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B. Allowed regions shrink: Correct. Steric repulsion from -NH(CH3) eliminates portions of the plot, notably the bottom-left quadrant (α-helix region), reducing overall conformational flexibility.
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C. Allowed regions expand: Incorrect. Expansion occurs in cases like glycine (no β-carbon) or proline relaxation, but bulkier N-substitution imposes stricter limits, not broader access.
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D. It depends on the specific amino acid side chains: Incorrect for backbone changes. While side chains influence plots (e.g., valine restricts more than glycine), the primary effect here is from N-methyl steric hindrance, consistent across residues.
Implications for Protein Structure
This modification mimics effects seen in peptidomimetics, where N-methylation enhances stability but reduces helical propensity, useful in drug design. In proteins, it would favor β-sheet or polyproline-like structures, shrinking core allowed regions by 20-30% in simulations. CSIR NET aspirants note: focus on steric maps for such questions.
