Protein folding and model generation MCQs With Answer

Protein folding and model generation MCQs With Answer

This quiz set covers essential concepts of protein folding and computational model generation tailored for M.Pharm students. It emphasizes thermodynamics and kinetics of folding, molecular chaperones, experimental structure determination techniques, and detailed aspects of in silico structure prediction—comparative modeling, threading, ab initio approaches, and model refinement. You will also encounter model validation metrics, force fields, solvation models, and enhanced sampling methods used in molecular dynamics. These questions are designed to deepen understanding relevant to drug design, structural analysis, and interpretation of computational models, helping bridge theoretical knowledge with practical workflows used in modern bioinformatics and computational biotechnology.

Q1. Which principle states that the native structure of a protein is determined by its amino acid sequence?

• Chaperone-assisted folding hypothesis
• Thermodynamic hypothesis (Anfinsen’s dogma)
• Energy landscape theory
• Lock-and-key model

Correct Answer: Thermodynamic hypothesis (Anfinsen’s dogma)

Q2. How is the protein folding energy landscape commonly described?

• As a single flat energy surface with one pathway to the native state
• As a funnel-shaped landscape with many local minima leading to the native state
• As a strictly monotonic decrease in energy without barriers
• As a random high-dimensional space with no bias toward native conformation

Correct Answer: As a funnel-shaped landscape with many local minima leading to the native state

Q3. What is the primary thermodynamic driving force for the burial of nonpolar residues during folding?

• Hydrogen bonding between backbone atoms
• Hydrophobic effect due to release of ordered water
• Formation of disulfide bridges
• Electrostatic attraction between charged side chains

Correct Answer: Hydrophobic effect due to release of ordered water

Q4. What is the main role of molecular chaperones in protein folding?

• To change the primary amino acid sequence
• To prevent aggregation and assist folding, often in an ATP-dependent manner
• To permanently bind unfolded proteins and inhibit folding
• To catalyze peptide bond formation during translation

Correct Answer: To prevent aggregation and assist folding, often in an ATP-dependent manner

Q5. What characterizes a two-state folding protein?

• Folding occurs through many stable intermediates detectable by spectroscopy
• Only unfolded and native states are significantly populated with single-exponential kinetics
• Folding requires chaperones and cannot proceed spontaneously
• Folding involves irreversible aggregation as a necessary intermediate

Correct Answer: Only unfolded and native states are significantly populated with single-exponential kinetics

Q6. Which structural change is commonly associated with amyloid formation in misfolding diseases?

• Increase in alpha-helical content forming soluble oligomers
• Transition to beta-sheet-rich fibrils that aggregate extracellularly
• Complete unfolding followed by proteolytic degradation
• Formation of disulfide-linked dimers only

Correct Answer: Transition to beta-sheet-rich fibrils that aggregate extracellularly

Q7. Which experimental technique is best suited for estimating a protein’s overall secondary structure content rapidly?

• Mass spectrometry
• Circular dichroism spectroscopy
• Electron microscopy
• Surface plasmon resonance

Correct Answer: Circular dichroism spectroscopy

Q8. Which method typically yields atomic-resolution structures of proteins when suitable crystals can be obtained?

• Small-angle X-ray scattering (SAXS)
• X-ray crystallography
• Analytical ultracentrifugation
• Dynamic light scattering

Correct Answer: X-ray crystallography

Q9. What is the fundamental assumption behind homology (comparative) modeling?

• Protein structure cannot be inferred from sequence alone
• Proteins with similar sequences adopt similar 3D structures
• All proteins fold into a limited number of identical folds regardless of sequence
• Secondary structure prediction is sufficient for full 3D modeling

Correct Answer: Proteins with similar sequences adopt similar 3D structures

Q10. When is threading (fold recognition) typically preferred over simple sequence-based homology modeling?

• When a high-identity template is available (>70% sequence identity)
• When the target has no known fold and ab initio is impossible
• When sequence identity to known structures is low but a compatible fold may exist
• When experimental NMR data are available for the target

Correct Answer: When sequence identity to known structures is low but a compatible fold may exist

Q11. Which statement best describes ab initio protein structure prediction?

• It constructs models solely by copying a template structure
• It predicts structure from sequence using physics-based force fields and extensive sampling without templates
• It refines homology models using experimental restraints only
• It uses only secondary structure prediction without 3D assembly

Correct Answer: It predicts structure from sequence using physics-based force fields and extensive sampling without templates

Q12. Which software is widely used for comparative (homology) modeling by satisfaction of spatial restraints?

• GROMACS
• Modeller
• AutoDock
• BLAST

Correct Answer: Modeller

Q13. Which modeling package is well known for fragment assembly and de novo structure prediction?

• PSI-BLAST
• Rosetta
• Phenix
• Clustal Omega

Correct Answer: Rosetta

Q14. How does I-TASSER generally generate protein models?

• By pure ab initio molecular dynamics with no template use
• By combining threading to identify templates followed by iterative fragment assembly simulations
• By using only experimental NMR restraints provided by the user
• By homology modeling restricted to identical sequences

Correct Answer: By combining threading to identify templates followed by iterative fragment assembly simulations

Q15. Which validation tool assesses the stereochemical quality of backbone dihedral angles in a protein model?

• Ramachandran plot
• BLAST E-value
• Hydropathy plot
• Root-mean-square fluctuation (RMSF)

Correct Answer: Ramachandran plot

Q16. What does RMSD measure when comparing two protein structures?

• The correlation of secondary structure assignments
• The average atomic displacement between equivalent atoms after optimal superposition
• The total number of hydrogen bonds formed
• The solvent-accessible surface area difference

Correct Answer: The average atomic displacement between equivalent atoms after optimal superposition

Q17. Why is GDT-TS often preferred over RMSD for assessing model quality in CASP?

• GDT-TS measures sequence identity while RMSD does not
• GDT-TS is less sensitive to local outliers and better reflects overall topology correctness
• GDT-TS is faster to compute but less informative
• GDT-TS only considers sidechain positions whereas RMSD considers backbone

Correct Answer: GDT-TS is less sensitive to local outliers and better reflects overall topology correctness

Q18. What is the main purpose of energy minimization in model refinement?

• To explore all possible conformations exhaustively
• To relieve steric clashes and find a nearby local energy minimum
• To convert all beta strands into alpha helices
• To predict ligand binding affinity directly

Correct Answer: To relieve steric clashes and find a nearby local energy minimum

Q19. Which statement correctly contrasts explicit and implicit solvation models?

• Implicit models include individual water molecules while explicit treat solvent as continuum
• Explicit solvation models include individual water molecules and are more computationally expensive but more accurate
• Implicit models are always more accurate than explicit models
• Explicit models cannot model ionic strength effects

Correct Answer: Explicit solvation models include individual water molecules and are more computationally expensive but more accurate

Q20. Which enhanced sampling technique exchanges configurations among replicas at different temperatures to improve conformational sampling?

• Steered molecular dynamics (SMD)
• Replica exchange molecular dynamics (REMD)
• Normal mode analysis (NMA)
• Metadynamics without exchange

Correct Answer: Replica exchange molecular dynamics (REMD)

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