Backbone construction and modeling MCQs With Answer

Backbone construction and modeling MCQs With Answer

Introduction: This collection of multiple-choice questions focuses on backbone construction and modeling of protein structures, tailored for M. Pharm students studying Bioinformatics and Computational Biotechnology. The questions cover fundamental concepts such as backbone geometry, phi/psi dihedral angles, Ramachandran analysis, Cα-to-backbone reconstruction, loop modeling, fragment assembly, force fields, and practical tools like MODELLER and Rosetta. Each item tests both theoretical understanding and practical implications for drug design, structure prediction, and molecular simulations. Use these questions to reinforce mastery of backbone-building strategies, limitations of modeling methods, and interpretation of structural validation metrics in the context of pharmaceutical research.

Q1. What are the backbone dihedral angles that primarily define protein backbone conformation?

• Chi1 and Chi2
• Phi and Psi
• Omega and Tau
• Alpha and Beta

Correct Answer: Phi and Psi

Q2. Which plot is routinely used to evaluate the sterically allowed regions of backbone phi/psi angles in a protein?

• B-factor plot
• Hydropathy plot
• Ramachandran plot
• Contact map

Correct Answer: Ramachandran plot

Q3. In Cα-trace to backbone reconstruction, which additional local information is most commonly used to place N, C, and O atoms?

• Side-chain rotamer libraries
• Predicted B-factors
• Standard peptide geometry and ideal bond lengths/angles
• Solvent accessibility profiles

Correct Answer: Standard peptide geometry and ideal bond lengths/angles

Q4. Which computational method builds protein backbones by assembling short structural fragments derived from known structures?

• Molecular dynamics with explicit solvent
• Fragment assembly (Rosetta-style)
• Homology modeling via threading only
• Quantum mechanical optimization

Correct Answer: Fragment assembly (Rosetta-style)

Q5. During homology modeling, the backbone regions with low sequence identity or insertions/deletions are typically refined by which process?

• Loop modeling
• Side-chain pruning
• Global sequence alignment
• Energy decomposition analysis

Correct Answer: Loop modeling

Q6. Which angle is usually constrained close to 180° in peptide bonds, limiting backbone flexibility?

• Phi (φ)
• Psi (ψ)
• Omega (ω)
• Chi (χ)

Correct Answer: Omega (ω)

Q7. Which force field component is most critical to avoid steric clashes when constructing a protein backbone?

• Bond stretching term
• Angle bending term
• Van der Waals (Lennard-Jones) term
• Implicit solvent term

Correct Answer: Van der Waals (Lennard-Jones) term

Q8. MODELLER primarily uses which approach to generate backbone conformations in comparative modeling?

• Template-based spatial restraints and satisfaction by optimization
• Ab initio fragment assembly without templates
• Pure molecular dynamics simulated annealing
• Quantum mechanical energy minimization

Correct Answer: Template-based spatial restraints and satisfaction by optimization

Q9. What is the purpose of applying dihedral angle restraints during backbone modeling?

• To increase solvent exposure of polar residues
• To enforce experimentally observed local geometry and reduce conformational search space
• To convert alpha helices into beta sheets
• To randomly sample side-chain rotamers

Correct Answer: To enforce experimentally observed local geometry and reduce conformational search space

Q10. In loop modeling, ab initio methods differ from knowledge-based methods mainly because they:

• Use only experimental NMR data
• Generate conformations from physical energy and sampling without relying on library fragments
• Depend exclusively on homology templates
• Only optimize side-chain conformations

Correct Answer: Generate conformations from physical energy and sampling without relying on library fragments

Q11. Which validation metric assesses local backbone geometry by comparing torsion angles to favored regions?

• MolProbity clashscore
• Ramachandran favored percentage
• Root-mean-square deviation (RMSD) of atomic positions
• Hydrophobic moment

Correct Answer: Ramachandran favored percentage

Q12. When reconstructing a backbone from a Cα trace, which mathematical representation is often used to express backbone geometry compactly?

• Cartesian coordinates only
• Contact frequency matrices
• Internal coordinates (bond lengths, bond angles, dihedral angles)
• Hydropathy index vectors

Correct Answer: Internal coordinates (bond lengths, bond angles, dihedral angles)

Q13. Normal mode analysis applied to protein backbones is used primarily to:

• Calculate side-chain pKa values
• Explore low-frequency collective motions and conformational variability
• Predict binding free energies directly
• Determine primary sequence from structure

Correct Answer: Explore low-frequency collective motions and conformational variability

Q14. In backbone modeling, the term “decoy” typically refers to:

• A high-resolution experimentally solved structure
• An approximate modeled protein conformation generated during prediction
• A solvent molecule removed during preparation
• A scoring function used to rank structures

Correct Answer: An approximate modeled protein conformation generated during prediction

Q15. Fragment libraries used in fragment-assembly backbone building are derived from:

• Randomly generated peptide sequences
• Short segments of experimentally determined protein structures in the PDB
• Predicted secondary structures only
• Ab initio quantum calculations of dipeptides

Correct Answer: Short segments of experimentally determined protein structures in the PDB

Q16. Which technique can be combined with backbone modeling to incorporate experimental distance restraints (e.g., NOEs or crosslinks)?

• Distance geometry or restrained molecular dynamics
• Hydrophobicity scanning
• Secondary structure prediction by PSIPRED only
• Fourier transform infrared spectroscopy

Correct Answer: Distance geometry or restrained molecular dynamics

Q17. What is the principal advantage of coarse-grained backbone models in conformational sampling?

• They provide atomic-level detail for ligand docking
• They reduce degrees of freedom to allow faster exploration of large-scale motions
• They enforce exact experimental coordinates
• They eliminate the need for energy functions

Correct Answer: They reduce degrees of freedom to allow faster exploration of large-scale motions

Q18. During backbone refinement, energy minimization is performed mainly to:

• Maximize RMSD to the template
• Resolve steric clashes and relax geometry to a local energy minimum
• Introduce novel secondary structure elements
• Randomize dihedral angles for sampling

Correct Answer: Resolve steric clashes and relax geometry to a local energy minimum

Q19. Threading-based backbone modeling is particularly useful when:

• There is a high-identity template available
• The target sequence has no detectable homologs in the PDB but folds into a known fold
• Only side chains need modeling
• Predicting solvent-accessible surface area only

Correct Answer: The target sequence has no detectable homologs in the PDB but folds into a known fold

Q20. In constructing peptide backbone coordinates from predicted secondary structure, which constraint helps ensure realistic helix geometry?

• Enforcing phi ~ -60° and psi ~ -45° for alpha-helical residues
• Setting all omega angles to 90°
• Randomizing all chi angles
• Assigning beta-sheet torsions to all residues

Correct Answer: Enforcing phi ~ -60° and psi ~ -45° for alpha-helical residues

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