Analyzing docking results MCQs With Answer

Analyzing docking results MCQs With Answer is a concise quiz set designed for M.Pharm students to strengthen understanding of molecular docking output interpretation. This collection emphasizes practical evaluation of docking poses, scoring functions, pose validation and post-docking analyses such as rescoring, clustering, RMSD evaluation, and free energy estimation. Each question focuses on concepts and pitfalls encountered when translating docking scores into reliable predictions for lead optimization, including treatment of water molecules, protonation states, metal coordination, and validation metrics like enrichment and ROC-AUC. Use these MCQs to test and refine your ability to critically assess docking outcomes and improve structure-based drug design workflows.

Q1. Which metric is most commonly used to quantify the similarity between a predicted docking pose and an experimental ligand conformation?

• Binding energy score
• Hydrogen bond count
• Root-mean-square deviation (RMSD)
• Hydrophobic surface area

Correct Answer: Root-mean-square deviation (RMSD)

Q2. A docking program returns a very favorable docking score for a ligand, but the ligand shows severe torsional strain; what does this suggest?

• The ligand is definitely a potent binder in vitro
• The docking score may be overestimated due to ligand strain
• The protein structure is incorrectly modeled
• The ligand probably forms covalent bonds with the protein

Correct Answer: The docking score may be overestimated due to ligand strain

Q3. Which scoring function type relies on parameters derived from experimental binding data and weighted empirical terms?

• Force-field-based scoring
• Empirical scoring function
• Knowledge-based scoring function
• Quantum mechanical scoring

Correct Answer: Empirical scoring function

Q4. In virtual screening validation, which metric assesses how well actives are found early in the ranked list?

• RMSD
• Enrichment factor (EF)
• Solvent accessible surface area
• Number of rotatable bonds

Correct Answer: Enrichment factor (EF)

Q5. Which post-docking rescoring method estimates more physically realistic binding free energies by including solvation and entropic approximations?

• Grid-based scoring
• MM-GBSA (Molecular Mechanics – Generalized Born Surface Area)
• Simple hydrogen bond counting
• Lipophilicity scoring

Correct Answer: MM-GBSA (Molecular Mechanics – Generalized Born Surface Area)

Q6. What is the main limitation of relying solely on raw docking scores for hit selection?

• Docking scores are independent of ligand chemistry
• Docking scores do not account for entropic contributions and solvent effects accurately
• Docking scores always overestimate binding affinities
• Docking scores measure chemical reactivity instead of binding

Correct Answer: Docking scores do not account for entropic contributions and solvent effects accurately

Q7. During analysis, you observe two clusters of poses separated by >2 Å RMSD; what does clustering of docking poses typically reveal?

• Protein denaturation states
• Distinct binding modes or conformational families
• Number of hydrogen bonds only
• Ligand pKa values

Correct Answer: Distinct binding modes or conformational families

Q8. Which interaction type is often underrepresented in many docking scoring functions but can be critical for binding to metalloproteins?

• Hydrophobic interactions
• Pi–pi stacking
• Metal coordination geometry and ligand-metal specific terms
• Van der Waals contacts

Correct Answer: Metal coordination geometry and ligand-metal specific terms

Q9. Why is considering multiple protonation states and tautomers of a ligand important in docking and result analysis?

• Protonation only affects ligand color in visualization
• Different states can change hydrogen bonding patterns and binding affinities
• Docking algorithms automatically test all protonation states
• Protonation states are irrelevant for hydrophobic pockets

Correct Answer: Different states can change hydrogen bonding patterns and binding affinities

Q10. When validating docking poses against an X-ray structure, which RMSD cutoff is commonly used to consider a pose as correctly reproduced?

• ≤0.5 Å
• ≤2.0 Å
• ≤5.0 Å
• ≤10.0 Å

Correct Answer: ≤2.0 Å

Q11. What does consensus scoring aim to achieve when analyzing docking results?

• Combine multiple scoring functions to reduce false positives and increase reliability
• Average all docking poses geometrically
• Generate new ligand conformers from consensus
• Replace experimental binding assays

Correct Answer: Combine multiple scoring functions to reduce false positives and increase reliability

Q12. A docking result shows strong predicted binding but the ligand forms no interactions with known key active site residues. What is the likely interpretation?

• The ligand is guaranteed to be active
• The docking pose may be non-physical or a false positive
• The active site residues are not important
• The scoring function always ignores interactions

Correct Answer: The docking pose may be non-physical or a false positive

Q13. Which of the following analyses helps identify water molecules that mediate ligand–protein interactions and may be important to retain or displace?

• Interaction fingerprinting and water mapping
• Counting rotatable bonds
• Calculating molecular weight only
• Clustering based solely on ligand RMSD

Correct Answer: Interaction fingerprinting and water mapping

Q14. What is a primary purpose of post-docking local minimization or short molecular dynamics refinement of docking poses?

• To increase docking score artificially
• To relieve steric clashes and allow induced fit adjustments improving realism
• To change ligand chemistry
• To reduce computational cost

Correct Answer: To relieve steric clashes and allow induced fit adjustments improving realism

Q15. In enrichment studies, what does an ROC-AUC value close to 1 indicate?

• Poor discrimination between actives and inactives
• Random performance equivalent to chance
• Excellent discrimination between actives and decoys
• Insufficient ligand conformers

Correct Answer: Excellent discrimination between actives and decoys

Q16. Interaction fingerprints derived from docking results are useful because they:

• Provide a 3D printed model of the complex
• Summarize per-residue contacts enabling rapid comparison of poses and SAR trends
• Replace the need for experimental validation
• Measure absolute binding free energy directly

Correct Answer: Summarize per-residue contacts enabling rapid comparison of poses and SAR trends

Q17. Which factor is NOT typically captured well by most docking scoring functions and can lead to mis-ranking of ligands?

• Electrostatic interactions
• Desolvation penalties and conformational entropy changes
• Hydrogen bonding geometry
• Van der Waals complementarity

Correct Answer: Desolvation penalties and conformational entropy changes

Q18. When interpreting docking results for a flexible binding site, which strategy improves sampling of realistic poses?

• Use a single rigid receptor conformation only
• Include receptor flexibility with ensemble docking or induced-fit protocols
• Reduce ligand conformers to one rigid form
• Ignore water molecules entirely

Correct Answer: Include receptor flexibility with ensemble docking or induced-fit protocols

Q19. A decoy set in virtual screening is used primarily to:

• Provide known binders to calibrate docking
• Test the ability of a docking protocol to discriminate true actives from similar non-binders
• Increase the number of positive results
• Measure protein stability

Correct Answer: Test the ability of a docking protocol to discriminate true actives from similar non-binders

Q20. Which analysis helps detect if a high-scoring pose is stabilized mainly by unrealistic close contacts or steric overlaps?

• Visual inspection combined with clash detection and per-atom interaction energy analysis
• Counting the number of aromatic rings only
• Measuring ligand molecular weight
• Assessing docking runtime

Correct Answer: Visual inspection combined with clash detection and per-atom interaction energy analysis

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