Conformational analysis in molecular modeling MCQs With Answer

Introduction: Conformational analysis in molecular modeling is the study of how molecules adopt different shapes (conformers) through rotation around single bonds and ring flips. For B. Pharm students, understanding conformational preferences, torsional strain, steric hindrance, and energy profiles is essential for predicting bioactive conformations, drug–receptor interactions, and pharmacokinetic properties. Key concepts include Newman projections, staggered vs. eclipsed forms, axial vs. equatorial positions in cyclohexane, and computational methods like molecular mechanics and quantum calculations. Mastery of conformational analysis aids rational drug design and formulation. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is conformational analysis?

• The study of different spatial arrangements (conformers) accessible by rotation around single bonds
• The study of permanent connectivity changes in a molecule
• The analysis of reaction mechanisms involving bond breaking
• The measurement of optical rotation in chiral drugs

Correct Answer: The study of different spatial arrangements (conformers) accessible by rotation around single bonds

Q2. Which projection is most useful for visualizing rotations about carbon–carbon single bonds?

• Fischer projection
• Haworth projection
• Newman projection
• Chair projection

Correct Answer: Newman projection

Q3. In a Newman projection, which conformation has lower torsional strain?

• Eclipsed conformation
• Staggered conformation
• Planar conformation
• Twisted-planar conformation

Correct Answer: Staggered conformation

Q4. For ethane, the energy barrier to rotation about the C–C bond arises primarily from:

• Angle strain in bond angles
• Torsional strain due to H–H eclipsing interactions
• Electrostatic attractions between hydrogens
• Conjugation with a double bond

Correct Answer: Torsional strain due to H–H eclipsing interactions

Q5. In butane, the lowest energy staggered conformation is called:

• Gauche conformation
• Anti conformation
• Eclipsed conformation
• Skew-boat conformation

Correct Answer: Anti conformation

Q6. The gauche conformation in butane refers to a dihedral angle of approximately:

• 0°
• 60°
• 120°
• 180°

Correct Answer: 60°

Q7. Which term describes the destabilization caused by nonbonded atoms coming into close proximity?

• Torsional strain
• Angle strain
• Steric hindrance (van der Waals repulsion)
• Resonance stabilization

Correct Answer: Steric hindrance (van der Waals repulsion)

Q8. In cyclohexane, the most stable conformation is:

• Boat conformation
• Chair conformation
• Planar hexagon
• Envelope conformation

Correct Answer: Chair conformation

Q9. In a cyclohexane chair, substituents prefer which position to minimize 1,3-diaxial interactions?

• Axial position
• Equatorial position
• Planar position
• Bridgehead position

Correct Answer: Equatorial position

Q10. A ring flip in cyclohexane interconverts axial and equatorial substituents by:

• Breaking and reforming bonds
• Rotation about a C–C single bond outside the ring
• A conformational rearrangement without bond cleavage
• Salt formation and recrystallization

Correct Answer: A conformational rearrangement without bond cleavage

Q11. The gauche effect often seen in 1,2-difluoroethane is due to:

• Increased steric repulsion between fluorines
• Hyperconjugation and favorable orbital interactions
• Hydrogen bonding between fluorines
• Loss of aromaticity

Correct Answer: Hyperconjugation and favorable orbital interactions

Q12. Which computational method is fastest for large-scale conformational searches in drug molecules?

• Ab initio quantum mechanics
• Density functional theory (DFT)
• Molecular mechanics (force fields)
• High-level coupled cluster

Correct Answer: Molecular mechanics (force fields)

Q13. Which force field is commonly used for small-molecule conformational studies in medicinal chemistry?

• MMFF (Merck Molecular Force Field)
• Hartree–Fock
• DFT-B3LYP
• CCSD(T)

Correct Answer: MMFF (Merck Molecular Force Field)

Q14. Potential energy surface (PES) maps are useful because they:

• Show only bond lengths of a molecule
• Depict energy changes as a function of molecular coordinates (e.g., dihedral angles)
• Measure experimental solubility
• Indicate optical activity directly

Correct Answer: Depict energy changes as a function of molecular coordinates (e.g., dihedral angles)

Q15. Which dihedral angle corresponds to the eclipsed conformation in ethane?

• 60°
• 120°
• 0°
• 180°

Correct Answer: 0°

Q16. Conformers that can be interconverted by rotation about single bonds without breaking covalent bonds are called:

• Isomers
• Resonance structures
• Conformational isomers (conformers)
• Tautomers

Correct Answer: Conformational isomers (conformers)

Q17. Why is conformational analysis important in drug–receptor interactions?

• Only chemical formula matters for binding
• Bioactive conformation dictates how a drug fits and binds to a receptor
• It determines melting point only
• It predicts pH of the drug solution

Correct Answer: Bioactive conformation dictates how a drug fits and binds to a receptor

Q18. Which factor does NOT directly affect conformational preference?

• Steric interactions
• Electronic (hyperconjugation) effects
• Solvent polarity
• Atomic mass number

Correct Answer: Atomic mass number

Q19. In monosubstituted cyclohexane, a bulky substituent will most likely be found in which conformation?

• Axial to increase steric interaction
• Equatorial to minimize steric strain
• Planar to maximize conjugation
• Boat to form intramolecular hydrogen bonds

Correct Answer: Equatorial to minimize steric strain

Q20. Which term describes the energy difference between two conformers?

• Activation energy
• Conformational energy or ΔE between conformers
• Ionization potential
• Binding constant

Correct Answer: Conformational energy or ΔE between conformers

Q21. Which experimental technique can provide information about conformational populations in solution?

• NMR spectroscopy
• Mass spectrometry only
• IR spectroscopy only without any solvent effects
• Chromatography retention time alone

Correct Answer: NMR spectroscopy

Q22. Which of the following best describes a rotamer?

• A structural isomer with different connectivity
• A conformer resulting from rotation about a single bond
• An ionized form of a drug
• A conformer fixed by a double bond

Correct Answer: A conformer resulting from rotation about a single bond

Q23. In peptides, backbone φ and ψ dihedral angles determine:

• The primary sequence only
• The conformational secondary structure (α-helix, β-sheet)
• Only side-chain chirality
• pKa values exclusively

Correct Answer: The conformational secondary structure (α-helix, β-sheet)

Q24. Which interaction can stabilize a gauche conformer despite steric crowding?

• Unfavorable electrostatic repulsion
• Hyperconjugative or orbital interactions
• Loss of aromaticity
• Cleavage of a sigma bond

Correct Answer: Hyperconjugative or orbital interactions

Q25. Conformational locking in drug design is used to:

• Increase metabolic instability
• Restrict flexibility to favor a bioactive conformation and improve potency
• Reduce binding specificity
• Increase overall molecular weight only

Correct Answer: Restrict flexibility to favor a bioactive conformation and improve potency

Q26. Which descriptor quantifies the orientation between four sequentially bonded atoms?

• Bond length
• Bond angle
• Dihedral (torsion) angle
• Van der Waals radius

Correct Answer: Dihedral (torsion) angle

Q27. In substituted cyclopentane, envelope and twist conformations exist to reduce:

• Pi stacking
• Angle and torsional strain
• Ionic interactions
• Covalent bond strengths

Correct Answer: Angle and torsional strain

Q28. Which statement about conformational energy minima is true?

• They correspond to transition states
• They represent stable conformers with locally lowest energy on the PES
• They are always global maxima
• They indicate bond-breaking events

Correct Answer: They represent stable conformers with locally lowest energy on the PES

Q29. When predicting drug conformation in a receptor, which factor is most critical to include in modeling?

• Only gas-phase energy without solvent
• Both conformational energy and protein–ligand interaction energy including solvation
• Only molecular weight
• Only the melting point of the drug

Correct Answer: Both conformational energy and protein–ligand interaction energy including solvation

Q30. Which change converts one stereoisomer into another and is NOT a conformational change?

• Rotation around a single bond
• Ring flip of cyclohexane
• Breaking and re-forming bonds (e.g., inversion at a stereocenter)
• Rotation about a C–N single bond without bond cleavage

Correct Answer: Breaking and re-forming bonds (e.g., inversion at a stereocenter)

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