Threading and homology modeling for protein prediction MCQs With Answer

Introduction

Threading and homology modeling are essential computational approaches for predicting three-dimensional protein structures when experimental data are unavailable. For M.Pharm students, understanding these techniques is crucial because predicted protein structures enable structure-based drug design, virtual screening, and target validation. Homology modeling builds models based on known structures of homologous proteins, while threading (fold recognition) identifies compatible folds even with low sequence identity by matching sequences to structural templates. This quiz set reinforces core concepts—template selection, alignment quality, loop refinement, side-chain packing, model validation, and common software—helping students apply models reliably in pharmacological research.

Q1. Which statement best describes homology (comparative) modeling in protein structure prediction?

• Predicting structure solely from physico-chemical principles without templates
• Building a 3D model based on experimentally determined structures of homologous proteins
• Matching a sequence to a fold library regardless of sequence similarity
• Using small-molecule docking to infer protein conformation

Correct Answer: Building a 3D model based on experimentally determined structures of homologous proteins

Q2. Threading (fold recognition) is particularly useful when:

• Sequence identity between target and template is very high (>90%)
• Target and template share no detectable sequence similarity but possible structural similarity exists
• Only ligand information is available
• Experimental X-ray structures exist for the target

Correct Answer: Target and template share no detectable sequence similarity but possible structural similarity exists

Q3. Which tool is primarily designed for automated homology modeling using spatial restraints?

• PSI-BLAST
• Modeller
• Phyre2
• ProSA

Correct Answer: Modeller

Q4. A commonly accepted sequence identity threshold above which homology models are generally reliable for backbone conformation is:

• < 20%
• 20–30%
• 30–50%
• >50%

Correct Answer: >50%

Q5. Which of the following best explains the “twilight zone” in sequence-based modeling?

• The region of protein structure with extreme disorder
• Sequence identity range (≈20–35%) where homologous relationships are hard to detect
• Sequence length below which modeling fails
• Threshold of RMSD below which models are perfect

Correct Answer: Sequence identity range (≈20–35%) where homologous relationships are hard to detect

Q6. Which method provides profile–profile comparison and HMM–HMM alignments commonly used for remote homolog detection?

• ClustalW
• HHpred/HHsearch
• AutoDock
• MolProbity

Correct Answer: HHpred/HHsearch

Q7. In homology modeling, the most critical step that determines model quality is:

• Final energy minimization only
• Selection of an appropriate template and accurate target-template alignment
• Removing all water molecules from template structure
• Converting sequence to secondary structure predictions

Correct Answer: Selection of an appropriate template and accurate target-template alignment

Q8. Which scoring function is specifically associated with assessing models produced by Modeller?

• DOPE (Discrete Optimized Protein Energy)
• GROMOS force field
• BLAST E-value
• Clustal score

Correct Answer: DOPE (Discrete Optimized Protein Energy)

Q9. Which validation metric measures the average distance between corresponding atoms of two superimposed structures?

• RMSD (Root Mean Square Deviation)
• GDT-TS
• MolProbity score
• ProSA Z-score

Correct Answer: RMSD (Root Mean Square Deviation)

Q10. Loop modeling is important because loops often:

• Are always rigid and thus trivial to model
• Contribute to binding sites and functional specificity and are variable in conformation
• Do not affect ligand binding and can be ignored
• Are identical across all protein families

Correct Answer: Contribute to binding sites and functional specificity and are variable in conformation

Q11. Which server combines threading, assembly and refinement and is often used when templates are distant or absent?

• Swiss-Model
• I-TASSER
• Clustal Omega
• PSIPRED

Correct Answer: I-TASSER

Q12. For a homology model intended for docking studies, which refinement step is most crucial after building the backbone?

• Side-chain modeling and rotamer optimization at the binding site
• Removing disulfide bonds
• Converting all residues to alanine
• Deleting loop regions to reduce complexity

Correct Answer: Side-chain modeling and rotamer optimization at the binding site

Q13. Which database/classification system groups protein domain structures and helps in template selection?

• PubChem
• SCOP/CATH
• KEGG
• ChEMBL

Correct Answer: SCOP/CATH

Q14. A ProSA Z-score for a modeled protein significantly outside the range of scores for native proteins of similar size indicates:

• The model is likely of poor quality
• The protein is intrinsically more stable
• The model is guaranteed correct
• No useful information about quality

Correct Answer: The model is likely of poor quality

Q15. Which statement about threading Z-scores is true?

• A high positive Z-score means the template is unlikely to be correct
• A significantly better (higher) Z-score compared to other templates suggests a confident fold assignment
• Z-score only applies to sequence alignments, not structures
• Z-score indicates the number of helices in the fold

Correct Answer: A significantly better (higher) Z-score compared to other templates suggests a confident fold assignment

Q16. Which of the following is NOT a common limitation of homology modeling?

• Poor accuracy when no close template exists
• Errors introduced by incorrect alignments
• Inability to predict novel folds without templates
• Guaranteed atomic-level accuracy for side chains in all cases

Correct Answer: Guaranteed atomic-level accuracy for side chains in all cases

Q17. Which technique improves detection of distant homologs by iteratively building a position-specific scoring matrix?

• PSI-BLAST
• AutoDock Vina
• MODELLER
• Ramachandran plotting

Correct Answer: PSI-BLAST

Q18. GDT-TS (Global Distance Test — Total Score) is preferred over RMSD in some assessments because it:

• Is always larger than RMSD
• Quantifies the fraction of residues within several distance cutoffs and is less sensitive to outliers
• Measures only side-chain accuracy
• Is independent of structure alignment

Correct Answer: Quantifies the fraction of residues within several distance cutoffs and is less sensitive to outliers

Q19. Which of the following is a widely used automated homology modeling web server for quick model generation?

• SWISS-MODEL
• GROMACS
• PyMOL
• ClustalW

Correct Answer: SWISS-MODEL

Q20. When using multiple templates for model building, the main advantage is:

• Always produces a lower DOPE score regardless of template quality
• Combines complementary structural features to improve model accuracy in different regions
• Reduces computational time dramatically
• Makes sequence alignment unnecessary

Correct Answer: Combines complementary structural features to improve model accuracy in different regions

Download