Hydrogen bonding and side-chain interactions MCQs With Answer

Hydrogen bonding and side-chain interactions MCQs With Answer is a focused study resource tailored for M.Pharm students tackling Bioinformatics and Computational Biotechnology. This blog presents concise, concept-driven multiple-choice questions that probe both fundamental and applied aspects of hydrogen bonds and side-chain interactions in biomolecules. Each question explores molecular geometry, energetics, role in protein folding, ligand binding, and computational detection methods such as force fields and scoring functions. Emphasis is placed on realistic scenarios in drug discovery, structural analysis, and mutation effects. Use these MCQs to reinforce theoretical knowledge, prepare for exams, and sharpen problem-solving skills relevant to molecular modelling and rational drug design.

Q1. Which of the following best describes the geometric criteria commonly used to define a strong biological hydrogen bond?

• Donor-acceptor distance ~2.7–3.2 Å and donor-hydrogen-acceptor angle >150°
• Donor-acceptor distance ~1.5–2.0 Å and donor-hydrogen-acceptor angle <90°
• Donor-acceptor distance >4.0 Å with any angle
• Only the presence of electronegative atoms regardless of distance

Correct Answer: Donor-acceptor distance ~2.7–3.2 Å and donor-hydrogen-acceptor angle >150°

Q2. In proteins, which side chain pair interaction is primarily stabilized by a salt bridge?

• Arginine and aspartate
• Phenylalanine and leucine
• Cysteine and methionine
• Tryptophan and tyrosine

Correct Answer: Arginine and aspartate

Q3. Which computational method most directly identifies hydrogen bonds from a static protein structure?

• Distance and angle-based geometric criteria scanning
• Molecular dynamics with explicit solvent only
• Sequence alignment algorithms
• Principal component analysis

Correct Answer: Distance and angle-based geometric criteria scanning

Q4. Which side-chain interaction is primarily driven by London dispersion forces and burial from solvent?

• Hydrophobic contacts between aliphatic residues
• Salt bridges between charged residues
• Hydrogen bonds between backbone atoms
• Pi-cation interactions with aromatic rings

Correct Answer: Hydrophobic contacts between aliphatic residues

Q5. Water-mediated hydrogen bonds in active sites are important because they:

• Can bridge ligand and protein, influencing binding affinity and specificity
• Always reduce ligand binding affinity
• Are irrelevant if a direct hydrogen bond exists
• Only occur in unfolded proteins

Correct Answer: Can bridge ligand and protein, influencing binding affinity and specificity

Q6. Which of the following side chains can act as both hydrogen bond donor and acceptor under physiological pH?

• Serine
• Leucine
• Phenylalanine
• Methionine

Correct Answer: Serine

Q7. In molecular mechanics force fields, hydrogen bond strength is typically modelled implicitly by:

• Electrostatic (partial charges) and van der Waals terms
• Explicit hydrogen bond harmonic restraint only
• Covalent bond stretching parameters
• Torsional angle potentials exclusively

Correct Answer: Electrostatic (partial charges) and van der Waals terms

Q8. Which aromatic side-chain interaction involves overlap of π-electron clouds between rings and contributes to specificity?

• Pi–pi stacking
• Hydrogen bonding
• Salt bridge
• Thioether linkage

Correct Answer: Pi–pi stacking

Q9. A conserved hydrogen-bond network in an enzyme active site commonly contributes to:

• Transition state stabilization and catalytic proton transfer
• Increasing global hydrophobicity
• Promoting random coil formation
• Preventing ligand entry into the site

Correct Answer: Transition state stabilization and catalytic proton transfer

Q10. Which statement about CH–π interactions is correct?

• They are weak but significant noncovalent stabilizers between aliphatic C–H and aromatic π systems
• They are equivalent in strength to covalent bonds
• They only form in the absence of solvent
• They require charged residues to occur

Correct Answer: They are weak but significant noncovalent stabilizers between aliphatic C–H and aromatic π systems

Q11. Which residue substitution is most likely to disrupt a backbone-side chain hydrogen bond that stabilizes an α-helix?

• Replacing alanine with proline
• Replacing valine with leucine
• Replacing serine with threonine
• Replacing aspartate with glutamate

Correct Answer: Replacing alanine with proline

Q12. In scoring ligand–protein interactions, a desolvation penalty is applied because:

• Breaking favorable ligand–water and protein–water hydrogen bonds costs free energy
• Hydrophobic interactions always provide energy without cost
• Only covalent interactions contribute to binding energy
• Solvent has no effect on binding thermodynamics

Correct Answer: Breaking favorable ligand–water and protein–water hydrogen bonds costs free energy

Q13. Which of the following best describes cooperativity in hydrogen-bond networks?

• Formation of one hydrogen bond can strengthen adjacent hydrogen bonds
• Hydrogen bonds always act independently with no mutual influence
• Cooperativity only occurs in ionic bonds
• Adding more hydrogen bonds decreases the overall stability

Correct Answer: Formation of one hydrogen bond can strengthen adjacent hydrogen bonds

Q14. Metal coordination to side chains (e.g., Zn2+ to histidine/cysteine) differs from hydrogen bonding mainly because:

• Metal coordination involves partial covalent/ionic character and specific coordination geometry
• Metal coordination is always weaker than hydrogen bonds
• Hydrogen bonds require a metal ion to form
• Metal coordination only occurs outside proteins

Correct Answer: Metal coordination involves partial covalent/ionic character and specific coordination geometry

Q15. Which of the following descriptors is most relevant when a computational algorithm ranks hydrogen bonding interactions for docking poses?

• Donor–acceptor distance and angle, and desolvation context
• Only the molecular weight of the ligand
• Sequence identity of unrelated protein regions
• Global RMSD without considering contacts

Correct Answer: Donor–acceptor distance and angle, and desolvation context

Q16. Disulfide bonds between cysteines contribute to protein stability primarily by:

• Restricting conformational entropy through covalent crosslinks
• Forming hydrogen bonds with water
• Acting as strong ionic interactions
• Increasing backbone flexibility

Correct Answer: Restricting conformational entropy through covalent crosslinks

Q17. Which effect would a mutation that replaces a buried polar side chain forming three hydrogen bonds with a nonpolar residue most likely have?

• Decrease in protein stability due to loss of buried hydrogen-bonding interactions
• Increase in catalytic activity by default
• No structural consequence because buried residues are irrelevant
• Guaranteed increase in solubility

Correct Answer: Decrease in protein stability due to loss of buried hydrogen-bonding interactions

Q18. In an MD simulation, monitoring hydrogen bond occupancy between a ligand and a residue provides information on:

• Persistence and fraction of simulation time the hydrogen bond is present
• Absolute binding free energy without further analysis
• Only the covalent bonding changes during simulation
• Sequence conservation across species

Correct Answer: Persistence and fraction of simulation time the hydrogen bond is present

Q19. Which side-chain interaction often contributes selectivity for cationic drugs binding to aromatic residues in proteins?

• Pi–cation interaction between aromatic ring and positively charged group
• Hydrophobic contact only between aliphatic chains
• Disulfide bond formation with the drug
• Backbone peptide bond cleavage

Correct Answer: Pi–cation interaction between aromatic ring and positively charged group

Q20. Which parameter is least useful when using a structure-based pharmacophore to capture hydrogen-bonding features?

• Overall protein sequence length
• Spatial coordinates of hydrogen bond donors/acceptors
• Directional vector (angle) of donor–hydrogen–acceptor
• Accessible surface and solvent exposure of the donor/acceptor

Correct Answer: Overall protein sequence length

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