Computional Structural Biology Flashcards
Select the correct statement regarding the use of protein crystals in X-ray diffraction.
A Proteins cannot scatter X-rays unless crystallized.
B Crystallization ensures proteins adopt their native conformations.
C Crystals eliminate background noise in the diffraction pattern.
D Crystallization creates a lattice that produces measurable diffraction patterns
D Crystallization creates a lattice that produces measurable diffraction patterns
In protein structure determination, electron density maps:
A Directly display the exact positions of all atoms in the protein.
B Are derived from processed diffraction data.
C Are used exclusively for small proteins.
D Represent theoretical electron distributions predicted from atomic models.
B Are derived from processed diffraction data.
In X-ray crystallography, when will constructive interference occur? (Select all that apply)
A X-ray waves diffracted from parallel crystal planes meet Bragg’s Law conditions.
B The path difference between scattered waves equals half a wavelength.
C The crystal lattice spacing is larger than the incident X-ray wavelength.
D The amplitude of diffracted waves cancels out.
A X-ray waves diffracted from parallel crystal planes meet Bragg’s Law conditions.
The process of building a protein structure from electron density requires:
A Iterative refinement of atomic coordinates against experimental data and geometric restraints.
B Direct mapping of amino acid side chains based on characteristic electron density shapes.
C Sequential tracing of the backbone followed by automated side chain placement.
D Real-time modification of atomic positions guided by difference density maps.
A Iterative refinement of atomic coordinates against experimental data and geometric restraints.
Select all advantages that Cryo-EM has over X-ray crystallography:
A Enables visualization of proteins in their native environment.
B Enables capture of multiple conformational states.
C Allows study of larger macromolecular complexes.
D Does not require solidifying the sample.
E Can always achieve superior resolution.
F Captures membrane proteins in lipid environments.
A Enables visualization of proteins in their native environment.
B Enables capture of multiple conformational states.
C Allows study of larger macromolecular complexes.
F Captures membrane proteins in lipid environments.
At which structural level are hydrogen bonds between backbone atoms primarily responsible for stabilizing regular conformations?
A Primary structure.
B Secondary structure.
C Tertiary structure.
D Both primary and tertiary structure
B Secondary structure.
In Single Particle Analysis (SPA) for Cryo-EM, three-dimensional reconstruction requires:
A Determination of particle orientations through projection matching and angular assignment.
B Averaging of all particle images regardless of their conformational states.
C Sequential merging of 2D class averages based on sample tilting angles.
D Direct conversion of 2D micrographs into 3D volumes using Fourier transforms
A Determination of particle orientations through projection matching and angular assignment.
Explain the technical challenges of studying intrinsically disordered proteins (IDPs) versus well-ordered proteins using experimental techniques.
IDPs lack a stable 3D structure under physiological conditions, unlike well-ordered proteins that fold
into specific shapes essential for their function. This inherent flexibility means that IDPs exist as
dynamic ensembles of conformations rather than a fixed structure.
X-ray crystallography requires the formation of well-ordered crystals, which is nearly impossible with
IDPs due to their structural heterogeneity.
Nuclear magnetic resonance (NMR) spectroscopy
faces difficulties because the multitude of overlapping signals from rapidly interconverting conformations complicates data interpretation.
Cryo-EM relies on averaging multiple images to resolve structures, but the conformational variability of IDPs leads to blurred results
Which energy landscape feature presents the main difficulty for predicting protein structures?
A The large number of possible conformations that increases exponentially with protein length.
B The flat energy landscape lacking significant energy barriers between conformations.
C The complex, rugged energy surface with numerous low-energy structures.
D The influence of temperature on the stability of different conformational states
C The complex, rugged energy surface with numerous low-energy structures.
When is homology modeling expected to give the most accurate structural predictions?
A When the template and target share over 90% sequence identity across conserved regions.
B When the template and target share less than 30% sequence identity but have similar functions.
C When the template and target share >65% sequence identity across the full protein length.
D When the template and target share 50% sequence identity with significant gaps and insertions.
C When the template and target share >65% sequence identity across the full protein length.
When would protein threading be the most appropriate approach for structure prediction?
A When the target has 15-25% sequence identity with known structures but predicted secondary
structure elements match existing folds.
B When the target sequence shows strong conservation of hydrophobic packing patterns despite
low overall sequence identity.
C When multiple sequence alignments reveal conserved structural motifs within a protein family.
D When remote homologs exist but their evolutionary relationship cannot be detected by sequence
comparison alone.
D When remote homologs exist but their evolutionary relationship cannot be detected by sequence
comparison alone.
How does modern coevolutionary analysis identify meaningful residue-residue contacts in protein
structures?
A By detecting conserved residues that are identical across different species.
B By separating direct evolutionary couplings from indirect correlations using statistical methods.
C Through random sampling of residue pairs in protein sequences.
D By predicting contacts based on amino acid likelihood for certain secondary structures.
B By separating direct evolutionary couplings from indirect correlations using statistical methods.
How do MD simulations enhance our understanding of protein dynamics?
A By providing static snapshots of proteins in their lowest energy states.
B By sampling the global energy minimum conformation of proteins.
C By using quantum mechanical methods to simulate bond-breaking and electron transfer events
within proteins.
D By generating time-resolved trajectories of each atom that capture both small-scale and largescale protein motions.
D By generating time-resolved trajectories of each atom that capture both small-scale and largescale protein motions.
How are protein force field parameters determined and optimized?
A By iteratively adjusting them to match quantum mechanical calculations of small molecules and
from experimental thermodynamic data.
B By training machine learning models on experimental protein structures and spectroscopy.
C By fitting them to high-level theoretical calculations and experimental vibrational spectra data.
D By tuning parameters to align with protein folding and unfolding free energy measurements.
A By iteratively adjusting them to match quantum mechanical calculations of small molecules and
from experimental thermodynamic data.
In force fields, chemical bonds are typically modeled as:
A Springs that can stretch and break, accounting for the energy needed to break bonds.
B Simple springs that can stretch and compress around their natural length.
C Connected springs that affect both bond lengths and angles together.
D Classical approximations based on quantum mechanical calculations.
B Simple springs that can stretch and compress around their natural length.
Why is selecting an appropriate time step crucial in MD simulations?
A The time step must be smaller than the shortest vibrational period to accurately capture atomic
motions.
B Larger time steps allow for faster simulations by skipping intermediate calculations without affecting accuracy.
C The time step determines how efficiently the simulation explores the potential energy surface of
the molecular system.
D The time step does not have any impact on the physical accuracy of the simulation results.
A The time step must be smaller than the shortest vibrational period to accurately capture atomic
motions.
How are dihedral angle potentials modeled in force fields?
A Using complex corrections based on quantum calculations between adjacent angles.
B With periodic energy functions that include patterns matching rotational symmetry.
C Through multiple cosine functions with optimized strengths and angles derived from detailed
energy profiles.
D By employing flexible spline functions that connect quantum reference points while maintaining
rotational consistency.
C Through multiple cosine functions with optimized strengths and angles derived from detailed
energy profiles.
A researcher is simulating how a protein and a molecule bind together and notices that the molecule
quickly leaves the binding site during the simulation. What change to the simulation settings could
help keep the molecule in the binding area?
A Slowly lower the solvent’s ability to reduce electric charges to make the attraction between the
molecule and the binding site stronger.
B Use adaptive time steps that become smaller where there are strong forces around the binding
site.
C Apply restrictions on the molecule’s position or use advanced sampling methods to keep it in the
binding site.
D Increase the range for non-bonded interactions and update the nearby particles list more often.
C Apply restrictions on the molecule’s position or use advanced sampling methods to keep it in the
binding site.
In simulations with periodic boundary conditions (PBC):
A The system uses elastic collisions at the edges to keep momentum but stops particles from escaping.
B Long-range forces are cut off at the box edges to save computing power and avoid errors from
particles interacting with themselves.
C Atoms that leave one side of the simulation box re-enter from the opposite side, keeping interactions continuous.
D Each particle interacts only with the nearest images of other particles within a set distance.
C Atoms that leave one side of the simulation box re-enter from the opposite side, keeping interactions continuous
The minimum elements needed to simulate a protein inside a cell include:
A Protein structure, explicit water molecules, and ions to balance the system’s overall charge.
B Protein structure using a model that doesn’t show individual water molecules but includes normal salt levels.
C Protein structure, explicit water molecules, ions at physiological concentration, and any required
cofactors.
D Protein structure with specific water molecules closely surrounding it and a variable that adjusts
for the overall solvent effects.
C Protein structure, explicit water molecules, ions at physiological concentration, and any required
cofactors.
Energy minimization is needed before running an MD simulation to:
A Optimize the system’s energy landscape to make sampling different shapes more efficient during
the main simulation.
B Relax local strains in bonds and angles while keeping the overall protein shape to start from a
stable configuration.
C Remove bad overlaps, unfavorable charge interactions, and high-energy shapes that could cause
calculation problems.
D Balance the water distribution around the protein while slowly removing restraints to keep the
system stable.
C Remove bad overlaps, unfavorable charge interactions, and high-energy shapes that could cause
calculation problems.
When preparing a protein structure, choosing the right protonation states is important because:
A They determine the strength of hydrogen bonds inside the protein and affect its local stability.
B They control electric interactions, affect the acidity levels of nearby parts, and can change how
the protein binds to other molecules.
C They change the local electric environment around certain parts and influence how protons move
in active sites.
D They manage the formation of salt bridges where the protein meets the solvent and affect the
overall charge in the simulation.
B They control electric interactions, affect the acidity levels of nearby parts, and can change how
the protein binds to other molecules.
A complete protein structure determined by X-ray crystallography with a resolution of 3.0 Å is:
A Suitable for MD simulations after refining side chain positions and backbone geometry.
B Limited in reliability because atomic positions are uncertain and loops might be missing.
C Good for MD simulations but needs additional modeling and validation.
D Directly usable for MD if combined with other data like Cryo-EM or NMR.
A Suitable for MD simulations after refining side chain positions and backbone geometry.
Observable properties in molecular systems are:
A Average values calculated from the system’s wave function over time for specific energy levels.
B Averages taken over all possible states, weighted by their likelihood at a stable temperature.
C Long-term averages of how variables change around their stable values.
D States sampled based on the assumption that all accessible states are equally likely
B Averages taken over all possible states, weighted by their likelihood at a stable temperature.
