Docking-based virtual screening MCQs With Answer

Introduction

Docking-based virtual screening is a core technique in structure-based drug design that uses molecular docking algorithms to predict ligand binding modes and estimate binding affinity for large compound libraries. For B. Pharm students, mastering docking concepts—such as protein and ligand preparation, scoring functions, flexible versus rigid docking, grid generation, and validation metrics—is essential for rational lead identification. Practical knowledge of docking workflows, common software (AutoDock, Glide, GOLD), enrichment metrics (ROC, AUC, EF), and pitfalls like protonation states, tautomerism, and water-mediated interactions improves screening success. This primer emphasizes applied understanding to bridge theory and pharmaceutical research. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the primary objective of docking-based virtual screening?

• To synthesize new drug molecules in the laboratory
• To predict the preferred orientation of a ligand when bound to a protein
• To determine pharmacokinetic properties experimentally
• To sequence the genome of a target organism

Correct Answer: To predict the preferred orientation of a ligand when bound to a protein

Q2. Which component of a docking workflow assigns numerical values estimating binding affinity?

• Grid generation
• Scoring function
• Conformer generation
• Protein expression

Correct Answer: Scoring function

Q3. Which docking approach allows movement of both ligand and selected protein side chains?

• Rigid docking
• Flexible ligand docking with rigid receptor
• Induced-fit (flexible receptor) docking
• Blind docking

Correct Answer: Induced-fit (flexible receptor) docking

Q4. Why is protonation state important in docking?

• It affects the color of the protein crystal
• It determines ligand solubility in organic solvents only
• It influences hydrogen bonding and electrostatic interactions in the binding site
• It is irrelevant because docking ignores charges

Correct Answer: It influences hydrogen bonding and electrostatic interactions in the binding site

Q5. Which metric assesses early recognition of active compounds in virtual screening?

• RMSD (Root Mean Square Deviation)
• Enrichment Factor (EF)
• pKa
• LogP

Correct Answer: Enrichment Factor (EF)

Q6. What does RMSD measure in docking validation?

• Difference in molecular weight between two ligands
• Positional deviation between predicted and experimental ligand poses
• Protein thermal stability
• Binding free energy in kcal/mol

Correct Answer: Positional deviation between predicted and experimental ligand poses

Q7. Which of the following is a commonly used open-source docking program?

• Glide
• AutoDock
• Schrödinger Maestro
• GOLD

Correct Answer: AutoDock

Q8. What is the purpose of generating a docking grid?

• To determine ADME properties
• To define the spatial region for ligand sampling and scoring
• To calculate the octanol-water partition coefficient
• To predict metabolism pathways

Correct Answer: To define the spatial region for ligand sampling and scoring

Q9. In virtual screening, what are “decoys” used for?

• To measure protein expression yields
• As inactive compounds resembling actives for benchmarking enrichment
• To calibrate mass spectrometers
• To increase ligand solubility during assays

Correct Answer: As inactive compounds resembling actives for benchmarking enrichment

Q10. Which factor is NOT typically considered during protein preparation for docking?

• Addition or removal of crystallographic waters based on relevance
• Assigning protonation states of ionizable residues
• Optimizing side-chain orientations and adding missing atoms
• Altering the primary amino acid sequence

Correct Answer: Altering the primary amino acid sequence

Q11. What is consensus scoring in virtual screening?

• Using multiple scoring functions to rank compounds
• Scoring ligands only by their molecular weight
• Applying a single docking program multiple times
• Ranking compounds by experimental solubility

Correct Answer: Using multiple scoring functions to rank compounds

Q12. Which type of scoring function includes explicit terms for entropy and solvation and often uses physics-based calculations?

• Empirical scoring functions
• Knowledge-based potentials
• Force-field or physics-based scoring
• Simple distance-based scoring

Correct Answer: Force-field or physics-based scoring

Q13. What does AUC (Area Under the ROC Curve) represent in virtual screening evaluation?

• The area of the binding pocket
• Overall ability of a method to discriminate actives from inactives
• Average docking time per ligand
• Absolute binding energy in kcal/mol

Correct Answer: Overall ability of a method to discriminate actives from inactives

Q14. Which ligand property is crucial when generating conformers for docking?

• Number of aromatic rings only
• Rotatable bonds and accessible torsional space
• Color and odor
• Storage temperature

Correct Answer: Rotatable bonds and accessible torsional space

Q15. Why might water molecules be included in docking?

• They always destabilize ligand binding
• They can mediate ligand–protein hydrogen bonds and influence binding thermodynamics
• They reduce computation time
• They change ligand chirality

Correct Answer: They can mediate ligand–protein hydrogen bonds and influence binding thermodynamics

Q16. What is blind docking?

• Docking without visualizing results
• Docking to the entire protein surface when the binding site is unknown
• Docking with all atoms frozen except hydrogens
• Docking only to the active site defined by a co-crystallized ligand

Correct Answer: Docking to the entire protein surface when the binding site is unknown

Q17. Which validation step checks whether a docking protocol can reproduce an experimentally observed ligand pose?

• ADME prediction
• Cross-docking and redocking with RMSD comparison
• Calculating LogP
• Protein expression analysis

Correct Answer: Cross-docking and redocking with RMSD comparison

Q18. What is a common limitation of docking scoring functions?

• They perfectly predict absolute binding free energy
• They may inadequately model entropic contributions and water effects
• They always require experimental NMR data
• They cannot rank ligands at all

Correct Answer: They may inadequately model entropic contributions and water effects

Q19. Which post-docking step can improve confidence in predicted binding modes by accounting for dynamics?

• Molecular dynamics (MD) simulation
• Thin-layer chromatography
• UV–Vis spectroscopy
• Standard PCR

Correct Answer: Molecular dynamics (MD) simulation

Q20. What is the role of enrichment curves in virtual screening?

• To plot ligand solubility versus pH
• To evaluate how many actives are found among top-ranked compounds
• To measure protein purity
• To calculate ligand synthesis cost

Correct Answer: To evaluate how many actives are found among top-ranked compounds

Q21. Which feature of a ligand often reduces docking accuracy if not correctly handled?

• Correct stereochemistry and tautomers
• Its melting point
• Manufacturer name
• Storage container type

Correct Answer: Correct stereochemistry and tautomers

Q22. What is cross-docking used to assess?

• Ability of docking to predict binding across different receptor conformations
• pKa shifts upon binding
• Rate of ligand synthesis
• Ligand fluorescence

Correct Answer: Ability of docking to predict binding across different receptor conformations

Q23. Which statement about flexible ligand sampling is true?

• Only a single rigid conformation of a ligand is considered
• Sampling explores multiple conformations to identify low-energy poses
• Flexibility is irrelevant in binding affinity
• Sampling always guarantees experimental activity

Correct Answer: Sampling explores multiple conformations to identify low-energy poses

Q24. Which molecular descriptor is often used as a filter before docking to remove undesirable compounds?

• Number of atoms in the protein
• Lipinski’s Rule of Five parameters like molecular weight and LogP
• Crystal packing density
• UV absorbance peak

Correct Answer: Lipinski’s Rule of Five parameters like molecular weight and LogP

Q25. What is the significance of a co-crystallized ligand in structure-based docking?

• It prevents docking software from running
• It helps define the binding site and validate docking parameters
• It always must be removed and ignored
• It determines the ligand’s melting point

Correct Answer: It helps define the binding site and validate docking parameters

Q26. In high-throughput virtual screening, what is a common strategy to reduce false positives?

• Ignore scoring ranks and pick randomly
• Use consensus scoring and apply ADMET filters
• Dock only one ligand
• Exclude all charged ligands

Correct Answer: Use consensus scoring and apply ADMET filters

Q27. Which descriptor indicates how well a docking pose reproduces key interactions observed in a reference complex?

• Binding site volume alone
• Interaction fingerprint (IFP) similarity
• Compound color
• Number of rotatable bonds

Correct Answer: Interaction fingerprint (IFP) similarity

Q28. What is induced-fit docking particularly useful for?

• Accounting for large receptor conformational changes upon ligand binding
• Increasing ligand molecular weight artificially
• Measuring boiling point
• Predicting synthetic routes

Correct Answer: Accounting for large receptor conformational changes upon ligand binding

Q29. Which preprocessing step helps avoid unrealistic ligand geometries during docking?

• Generating 3D conformations and energy minimization
• Removing all hydrogen atoms permanently
• Increasing temperature of the docking engine
• Converting the ligand to a polymer

Correct Answer: Generating 3D conformations and energy minimization

Q30. Why is careful selection of the binding site grid box size important?

• Too small a box may miss relevant binding modes; too large increases false positives and computation time
• Box size only affects visualization, not results
• Larger boxes always guarantee better results regardless of cost
• Grid boxes determine ligand pKa

Correct Answer: Too small a box may miss relevant binding modes; too large increases false positives and computation time

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