Molecular docking fundamentals MCQs With Answer

Molecular docking fundamentals MCQs With Answer

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Molecular docking fundamentals MCQs With Answer introduces B. Pharm students to core concepts of computational drug design, including molecular docking, ligand–receptor interactions, binding affinity, scoring functions, docking algorithms, and virtual screening. This concise, keyword-rich guide explains pose prediction, RMSD evaluation, flexible versus rigid docking, scoring biases, and practical issues like protonation, tautomers, and water molecules in binding sites. Emphasis on scoring methods (empirical, force-field, knowledge-based), validation strategies, and common docking tools prepares students for applied tasks in drug discovery. Clear definitions and focused questions reinforce learning and exam readiness. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the primary goal of molecular docking in drug discovery?

  • To synthesize new drug molecules in the lab
  • To predict the optimal binding pose and estimate binding affinity between a ligand and its target
  • To determine the pharmacokinetics of a drug in humans
  • To measure the toxicity of a compound experimentally

Correct Answer: To predict the optimal binding pose and estimate binding affinity between a ligand and its target

Q2. Which term describes the three-dimensional orientation of a ligand inside a receptor binding site?

  • Conformation
  • Pose
  • Topology
  • Pharmacophore

Correct Answer: Pose

Q3. Which of the following is a common unit for reporting docking binding energy estimates?

  • moles per liter (M)
  • kcal/mol
  • ppm
  • degrees Celsius (°C)

Correct Answer: kcal/mol

Q4. Root-mean-square deviation (RMSD) is used in docking primarily to:

  • Calculate binding free energy
  • Compare predicted ligand poses to experimental reference structures
  • Estimate solubility of a ligand
  • Determine the number of hydrogen bonds

Correct Answer: Compare predicted ligand poses to experimental reference structures

Q5. Which docking approach allows movement of ligand rotatable bonds but keeps the receptor rigid?

  • Flexible receptor docking
  • Rigid-body docking
  • Flexible-ligand docking
  • Induced-fit docking

Correct Answer: Flexible-ligand docking

Q6. Which scoring function type uses physical equations from molecular mechanics to estimate interaction energies?

  • Empirical scoring function
  • Knowledge-based scoring function
  • Force-field (physics-based) scoring function
  • Machine-learning scoring function

Correct Answer: Force-field (physics-based) scoring function

Q7. A more negative predicted binding free energy from docking generally implies:

  • Weaker binding affinity
  • Stronger, more favorable binding affinity
  • No binding at all
  • Higher molecular weight

Correct Answer: Stronger, more favorable binding affinity

Q8. Which algorithm type is commonly used for exploring ligand conformational space in docking?

  • Genetic algorithms
  • Thin-layer chromatography
  • NMR spectroscopy
  • Mass spectrometry

Correct Answer: Genetic algorithms

Q9. What is the purpose of defining a grid box in grid-based docking methods?

  • To compute solubility of ligand
  • To limit the search region to the binding site and accelerate scoring
  • To store experimental X-ray data
  • To determine the pKa of residues

Correct Answer: To limit the search region to the binding site and accelerate scoring

Q10. Which preparation step is essential before docking a ligand and receptor?

  • Removing all hydrogens from the structure
  • Assigning correct protonation states and adding hydrogens
  • Heating the protein to 100°C
  • Dissolving the protein in organic solvent

Correct Answer: Assigning correct protonation states and adding hydrogens

Q11. Induced-fit docking accounts for:

  • Ligand conformational changes only
  • Receptor conformational changes in response to ligand binding
  • Only solvent effects
  • The synthesis route of the ligand

Correct Answer: Receptor conformational changes in response to ligand binding

Q12. Which validation method checks whether a docking program can reproduce an experimentally observed ligand pose?

  • High-throughput screening
  • Re-docking (self-docking)
  • ADME prediction
  • Metabolic stability assay

Correct Answer: Re-docking (self-docking)

Q13. Knowledge-based scoring functions are derived primarily from:

  • Quantum mechanical calculations only
  • Statistical analysis of known protein–ligand complexes
  • Clinical trial outcomes
  • Surface tension measurements

Correct Answer: Statistical analysis of known protein–ligand complexes

Q14. In virtual screening, an enrichment factor evaluates:

  • How well docking prioritizes true actives over decoys
  • The molecular weight distribution of a library
  • The solubility of screened compounds
  • The color of compounds in plates

Correct Answer: How well docking prioritizes true actives over decoys

Q15. Role of crystallographic water molecules in docking is often:

  • Always ignored because they are irrelevant
  • Considered selectively since conserved waters can mediate ligand binding
  • Used to compute pKa values
  • To increase ligand molecular weight

Correct Answer: Considered selectively since conserved waters can mediate ligand binding

Q16. Which of these is an example of a popular open-source docking program?

  • AutoDock
  • Excel
  • Photoshop
  • SPSS

Correct Answer: AutoDock

Q17. Covalent docking differs from non-covalent docking because it:

  • Predicts only ionic interactions
  • Models formation of a covalent bond between ligand and target residue
  • Does not require receptor coordinates
  • Is used only for nucleic acids

Correct Answer: Models formation of a covalent bond between ligand and target residue

Q18. Which metric measures the ability of a docking method to rank actives above inactives across a dataset?

  • Partition coefficient (log P)
  • Receiver Operating Characteristic (ROC) AUC
  • Melting point
  • Partition coefficient (log D)

Correct Answer: Receiver Operating Characteristic (ROC) AUC

Q19. Which factor can introduce errors in docking predictions if not handled correctly?

  • Incorrect ligand tautomer or protonation state
  • Using 3D coordinates for the receptor
  • Including rotatable bonds in the ligand
  • Scoring functions with hydrogen bond terms

Correct Answer: Incorrect ligand tautomer or protonation state

Q20. Consensus scoring is used to:

  • Combine multiple scoring functions to improve prediction reliability
  • Reduce the ligand molecular weight
  • Generate synthetic routes
  • Predict ADME properties directly

Correct Answer: Combine multiple scoring functions to improve prediction reliability

Q21. Flexible receptor docking is more computationally expensive primarily because:

  • It ignores ligand conformations
  • It samples many receptor conformations as well as ligand poses
  • It uses lower grid resolution
  • It uses less accurate scoring functions

Correct Answer: It samples many receptor conformations as well as ligand poses

Q22. Which of the following is a common force field used for small-molecule geometry and energy calculations?

  • MMFF94
  • HPLC
  • ELISA
  • PCR

Correct Answer: MMFF94

Q23. Cross-docking is performed to assess what aspect of docking performance?

  • Ability to reproduce the same pose from identical structures only
  • Robustness of docking when ligands are docked into different receptor conformations
  • Solubility prediction accuracy
  • UV absorbance of ligands

Correct Answer: Robustness of docking when ligands are docked into different receptor conformations

Q24. Which statement about scoring functions is true?

  • They always provide experimentally accurate binding free energies
  • They are approximations and may rank poses incorrectly; validation is essential
  • They are unnecessary for virtual screening
  • They only evaluate covalent bonds

Correct Answer: They are approximations and may rank poses incorrectly; validation is essential

Q25. The term ‘decoy’ in virtual screening refers to:

  • A compound known to be highly active
  • An inactive compound used to test screening specificity
  • A computational artifact with no structure
  • An enzyme cofactor

Correct Answer: An inactive compound used to test screening specificity

Q26. Molecular docking combined with which technique can improve understanding of binding dynamics?

  • Molecular dynamics (MD) simulations
  • Infrared spectroscopy only
  • Paper chromatography
  • Thin-layer chromatography

Correct Answer: Molecular dynamics (MD) simulations

Q27. Which property is NOT directly predicted by standard molecular docking?

  • Binding pose
  • Estimated binding affinity
  • ADME (absorption, distribution, metabolism, excretion) profiles
  • Relative ranking of ligands in a library

Correct Answer: ADME (absorption, distribution, metabolism, excretion) profiles

Q28. Why is ligand conformer generation important before docking?

  • To increase molecular weight
  • To provide diverse low-energy ligand geometries for accurate pose prediction
  • To change the primary sequence of a protein
  • To remove polar groups

Correct Answer: To provide diverse low-energy ligand geometries for accurate pose prediction

Q29. Which practice improves confidence in virtual screening hits before experimental testing?

  • Relying on a single scoring function without inspection
  • Applying visual inspection, rescoring with multiple methods, and short MD refinement
  • Ignoring protein preparation
  • Selecting the highest molecular weight compounds only

Correct Answer: Applying visual inspection, rescoring with multiple methods, and short MD refinement

Q30. In context of docking, ‘pose clustering’ is used to:

  • Group similar predicted ligand orientations to identify common binding modes
  • Cluster proteins by sequence similarity
  • Perform experimental crystallization
  • Determine the pH of the buffer

Correct Answer: Group similar predicted ligand orientations to identify common binding modes

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