Rigid docking methods MCQs With Answer

Introduction: Rigid docking methods are computational approaches in molecular docking where both the receptor and ligand are treated as fixed, non‑flexible bodies to predict binding modes and relative binding affinity. Important for B.Pharm students, rigid docking simplifies complex protein‑ligand interactions, accelerating virtual screening, hit identification, and structure‑based drug design. Key concepts include search algorithms, scoring functions, shape complementarity, grid mapping, and pose ranking. While faster and useful for high‑throughput screens, rigid docking has limitations in accounting for induced fit and side‑chain mobility. Understanding its assumptions and appropriate applications is essential for interpreting results and integrating flexible refinement. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the main assumption of rigid docking methods?

• The receptor and ligand are both treated as completely non‑flexible during docking
• The ligand is flexible while the receptor undergoes large conformational changes
• Only solvent molecules are allowed to move during docking
• The binding pocket is continuously remodeled during docking

Correct Answer: The receptor and ligand are both treated as completely non‑flexible during docking

Q2. Which advantage is most associated with rigid docking compared to flexible docking?

• Higher accuracy for induced‑fit binding predictions
• Faster computational speed permitting large virtual screens
• Better modeling of side‑chain rearrangements
• Automatically accounts for water mediation in binding

Correct Answer: Faster computational speed permitting large virtual screens

Q3. Which metric is commonly used to compare predicted and experimental ligand poses in docking validation?

• Hydrogen bond count
• Root‑mean‑square deviation (RMSD)
• LogP value
• pKa shift

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

Q4. Which component is a key part of most rigid docking algorithms for evaluating poses?

• Sequence alignment score
• Scoring function estimating binding energy
• Chromatographic retention time
• Membrane permeability predictor

Correct Answer: Scoring function estimating binding energy

Q5. Grid‑based rigid docking typically uses grids to represent:

• The solvent dielectric constant only
• The receptor’s interaction potential at fixed positions
• Ligand conformational ensembles
• Time‑dependent dynamics of the protein

Correct Answer: The receptor’s interaction potential at fixed positions

Q6. Which search method is often used in rigid docking for efficient orientation sampling?

• Fast Fourier Transform (FFT) correlation techniques
• Molecular dynamics with explicit solvent
• Genetic algorithms with extensive side‑chain rotations
• Quantum Monte Carlo

Correct Answer: Fast Fourier Transform (FFT) correlation techniques

Q7. A common limitation of rigid docking is its inability to:

• Score thousands of compounds quickly
• Model ligand or receptor induced fit during binding
• Rank-order ligand poses by an energy estimate
• Use precomputed potential grids

Correct Answer: Model ligand or receptor induced fit during binding

Q8. Which application is rigid docking particularly well suited for?

• Final lead optimization where subtle conformational changes matter
• High‑throughput virtual screening to filter large libraries
• Predicting water network rearrangements in binding sites
• Modeling allosteric conformational transitions

Correct Answer: High‑throughput virtual screening to filter large libraries

Q9. In the context of rigid docking, a scoring function that combines electrostatic and van der Waals terms is used to estimate:

• The synthetic accessibility of the ligand
• Binding affinity or interaction quality
• Protein expression level
• The ligand’s metabolic stability

Correct Answer: Binding affinity or interaction quality

Q10. Which software was among the first developed for shape‑based rigid docking of small molecules into proteins?

• DOCK
• GROMACS
• Gaussian
• CHARMM

Correct Answer: DOCK

Q11. When using rigid docking, which pre‑docking step is critical for meaningful results?

• Ensuring correct protonation states and preparing the receptor structure
• Running full‑scale quantum calculations on the ligand
• Applying long molecular dynamics simulations for the ligand
• Cloning the protein into an expression vector

Correct Answer: Ensuring correct protonation states and preparing the receptor structure

Q12. How does shape complementarity contribute in rigid docking?

• By matching ligand pharmacokinetics to receptor metabolism
• By assessing how well ligand and binding site geometries fit without deformation
• By predicting off‑target toxicity
• By optimizing synthetic routes for ligand synthesis

Correct Answer: By assessing how well ligand and binding site geometries fit without deformation

Q13. Which of the following is a typical output of a rigid docking run?

• Enzyme kinetics Km and Vmax
• Ranked ligand poses with associated scores
• Experimental binding constants (Kd) measured in vitro
• Covalent binding reaction mechanisms

Correct Answer: Ranked ligand poses with associated scores

Q14. In validation of rigid docking protocols, a successful docking reproduces the crystallographic pose with RMSD typically below:

• 10 Å
• 5 Å
• 2 Å
• 0.1 Å

Correct Answer: 2 Å

Q15. Why might rigid docking produce false positives in virtual screening?

• Because it always models water molecules explicitly
• Because scoring functions and rigid treatments can misrank molecules that require induced fit
• Because it chemically modifies ligands during docking
• Because it simulates long timescale dynamics incorrectly

Correct Answer: Because scoring functions and rigid treatments can misrank molecules that require induced fit

Q16. Which refinement step is commonly applied after rigid docking to improve predicted complexes?

• Flexible side‑chain or limited ligand minimization using energy minimization or short MD
• Triple‑helix DNA binding simulation
• In vitro enzymatic assay prior to synthesis
• Protein sequencing

Correct Answer: Flexible side‑chain or limited ligand minimization using energy minimization or short MD

Q17. Which term describes the technique where multiple rigid receptor conformations are docked separately to account for receptor flexibility implicitly?

• Ensemble docking
• Quantum docking
• Homology docking
• Allosteric docking

Correct Answer: Ensemble docking

Q18. In rigid docking scoring, solvation effects are often approximated using:

• Explicit water molecules sampled during docking
• Implicit solvation models or desolvation penalties in the scoring function
• NMR restraints
• Protein folding free energy calculations

Correct Answer: Implicit solvation models or desolvation penalties in the scoring function

Q19. What is the impact of grid resolution in grid‑based rigid docking?

• Higher resolution grids increase geometric accuracy but require more computation
• Grid resolution affects only ligand pKa predictions
• Lower resolution grids always improve docking accuracy
• Grid resolution determines the protein expression level

Correct Answer: Higher resolution grids increase geometric accuracy but require more computation

Q20. Rigid docking is often the first step in a pipeline because it is:

• Always more accurate than experimental methods
• Computationally efficient for narrowing large libraries before detailed analysis
• Able to predict off‑target effects directly
• Required for protein purification

Correct Answer: Computationally efficient for narrowing large libraries before detailed analysis

Q21. Which interaction type is commonly evaluated in rigid docking scoring functions?

• Van der Waals contacts
• Glycosylation patterns
• mRNA expression correlations
• Chromatographic retention

Correct Answer: Van der Waals contacts

Q22. A practical way to improve rigid docking results without full flexibility is to:

• Ignore all hydrogen atoms during docking
• Use multiple receptor conformations or include key side‑chain rotamers
• Increase the ligand’s molecular weight artificially
• Dock in vacuum with no electrostatics

Correct Answer: Use multiple receptor conformations or include key side‑chain rotamers

Q23. Which of the following best describes a scoring function based on physics‑based terms?

• It uses empirical activity cliffs from SAR alone
• It combines van der Waals, electrostatics, and solvation energy terms derived from physical models
• It predicts ADME properties only
• It ranks compounds by molecular weight

Correct Answer: It combines van der Waals, electrostatics, and solvation energy terms derived from physical models

Q24. Which validation practice helps assess the reliability of a rigid docking workflow?

• Docking decoy sets and benchmarking enrichment metrics like ROC AUC
• Only docking a single ligand and reporting its score
• Using docking to predict protein tertiary structure from sequence
• Measuring ligand solubility in water experimentally

Correct Answer: Docking decoy sets and benchmarking enrichment metrics like ROC AUC

Q25. In protein–protein rigid docking, which factor is most critical for correct complex prediction?

• Sequence identity only
• Surface complementarity and correct orientation of rigid bodies
• Ligand tautomers
• Solubility of small molecules

Correct Answer: Surface complementarity and correct orientation of rigid bodies

Q26. Which of the following is a typical reason to follow rigid docking with rescoring using more sophisticated methods?

• To convert docking poses into synthetic routes
• To better estimate binding free energy by considering flexibility and solvation more accurately
• To determine protein primary sequence
• To increase docking throughput further

Correct Answer: To better estimate binding free energy by considering flexibility and solvation more accurately

Q27. When interpreting rigid docking scores, B.Pharm students should remember that scores are:

• Absolute experimental binding constants usable directly as Kd
• Relative estimates useful for rank‑ordering rather than exact affinities
• Unaffected by ligand protonation or tautomeric state
• Always predictive of in vivo efficacy

Correct Answer: Relative estimates useful for rank‑ordering rather than exact affinities

Q28. Which practice reduces bias when preparing ligands for rigid docking?

• Consistently generating correct protonation states, tautomers, and 3D conformers before docking
• Using only one arbitrary tautomer for all ligands
• Omitting hydrogen atoms from ligand files permanently
• Applying experimental HPLC conditions to ligand files

Correct Answer: Consistently generating correct protonation states, tautomers, and 3D conformers before docking

Q29. Which outcome suggests a rigid docking hit may require further flexible refinement?

• The predicted pose fits the pocket perfectly with no steric clashes
• High docking score but obvious steric overlaps with side‑chains in the static receptor
• The ligand is identical to the crystallographic ligand
• The docking run failed due to hardware error

Correct Answer: High docking score but obvious steric overlaps with side‑chains in the static receptor

Q30. For a B.Pharm student, the best strategy when rigid docking fails to reproduce known binding is to:

• Conclude that docking is worthless for drug design
• Consider receptor flexibility, check preparation steps, or use ensemble/flexible docking and rescoring
• Ignore experimental data and accept docking results
• Reduce the number of ligands screened to one

Correct Answer: Consider receptor flexibility, check preparation steps, or use ensemble/flexible docking and rescoring

Download