Protein Homology and Modeling Techniques
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Questions and Answers

What are orthologs?

  • Gene sequences that are identical in length and function.
  • Homologous sequences within a single species.
  • Gene variants that arise from environmental changes within a species.
  • Homologous sequences in different species originating from a common ancestor. (correct)
  • Which statement is true about paralogs?

  • They arise by gene duplication within a single species. (correct)
  • They are always responsible for different functions.
  • They arise from ancestral genes during speciation.
  • They are found only in eukaryotic organisms.
  • In the context of the provided content, how can you categorize RBP and lactoglobulin?

  • RBP is an ortholog, while lactoglobulin can be a paralog. (correct)
  • Both are orthologs found in different species.
  • Both are paralogs within the same species.
  • Both are examples of homologous sequences derived from gene duplication.
  • What does the presence of one dot versus two dots imply in the sequence alignment?

    <p>Similarity with varying degree; one for somewhat similar, two for very similar.</p> Signup and view all the answers

    Which of the following best describes the relationship between zebrafish and common carp in terms of gene families?

    <p>They are orthologs owing to their divergent evolution.</p> Signup and view all the answers

    What is the primary purpose of cryoprotectants in x-ray crystallography?

    <p>To prevent ice formation</p> Signup and view all the answers

    Why is it important for a crystal to be well-ordered in x-ray crystallography?

    <p>It allows for a clearer diffraction pattern</p> Signup and view all the answers

    At what temperature is the crystal typically cryocooled during x-ray diffraction experiments?

    <p>-150°C</p> Signup and view all the answers

    What is the repeating unit that forms the crystal in x-ray crystallography called?

    <p>Unit cell</p> Signup and view all the answers

    What is the first prerequisite for successfully solving a protein's three-dimensional structure using x-ray crystallography?

    <p>A well-ordered crystal</p> Signup and view all the answers

    What typically happens to most of the primary x-ray beam when it interacts with a crystal?

    <p>It passes through the crystal</p> Signup and view all the answers

    Which characteristic makes growing well-ordered crystals particularly challenging?

    <p>Irregular shapes of globular proteins</p> Signup and view all the answers

    What is produced from well-ordered protein crystals during x-ray diffraction?

    <p>Diffraction patterns recorded on film</p> Signup and view all the answers

    What is the primary goal of protein threading?

    <p>To find the correct sequence-structure alignment</p> Signup and view all the answers

    Which of the following is NOT a challenge in constructing c-alpha distance models?

    <p>Modeling proteins with greater than 30% sequence identity</p> Signup and view all the answers

    What technique does threading utilize to find an optimal fit for unknown protein sequences?

    <p>Replacing known sequence fragments with unknown sequences</p> Signup and view all the answers

    In which situation can comparative modeling be considered mature despite its need for improvement?

    <p>When solving practical problems in structural biology</p> Signup and view all the answers

    What is the primary aspect of the energy function used in protein threading?

    <p>It relies on knowledge or statistics</p> Signup and view all the answers

    Which automated server is NOT mentioned as a resource for homology modeling?

    <p>Foldit</p> Signup and view all the answers

    What typically resides in the inner cores of protein structures?

    <p>Alpha-helices and beta sheets</p> Signup and view all the answers

    Which of the following serves as a significant improvement for comparative modeling?

    <p>Improved optimizers and potential functions</p> Signup and view all the answers

    What does Bragg's law relate to in X-ray diffraction?

    <p>The relationship between reflection angle, plane distance, and wavelength.</p> Signup and view all the answers

    How can the distance between crystal planes (d) be determined?

    <p>Using the angle and known wavelength with Bragg's law.</p> Signup and view all the answers

    What is the correct expression for Bragg's law?

    <p>$2d·sinθ = λ$</p> Signup and view all the answers

    What characterizes Thomson scattering in the context of X-ray scattering?

    <p>It models the interaction of electromagnetic rays with free electrons.</p> Signup and view all the answers

    What happens to most X-ray beams when they hit a crystal?

    <p>Most of them reinforce each other in specific directions.</p> Signup and view all the answers

    What role does the distance (r) play in X-ray diffraction?

    <p>It helps calculate reflection angles of scattered rays.</p> Signup and view all the answers

    In geometry related to X-ray diffraction, what does the angle 2θ represent?

    <p>The angle formed between the primary and diffracted beams.</p> Signup and view all the answers

    What occurs when X-rays are reflected from different planes in a crystal?

    <p>They must satisfy Bragg's law.</p> Signup and view all the answers

    What is primarily responsible for generating distinct diffraction spots in x-ray crystallography?

    <p>Positive interference among x-rays</p> Signup and view all the answers

    Which mathematical technique is used to analyze diffraction patterns in crystallography?

    <p>Fourier transform</p> Signup and view all the answers

    What happens to the phase information in x-ray experiments?

    <p>It is lost during data collection</p> Signup and view all the answers

    In Multiple Isomorphous Replacement (MIR), why are heavy atoms introduced into the crystal?

    <p>To enhance the diffraction pattern</p> Signup and view all the answers

    For a crystal to be suitable for Multiple Isomorphous Replacement (MIR), what characteristic must it retain?

    <p>Isomorphism despite added heavy atoms</p> Signup and view all the answers

    Which property of a diffracted beam is proportional to the intensity of the recorded spot?

    <p>Amplitude</p> Signup and view all the answers

    What defines a diffracted beam along with its amplitude and wavelength?

    <p>Phase information</p> Signup and view all the answers

    What characterizes the requirement for the introduction of heavy-metal complexes in protein crystallography?

    <p>They must act as a new x-ray scatterer</p> Signup and view all the answers

    Study Notes

    Protein Homology and Modeling

    • Lactoglobulin and RBP (Retinol-Binding Protein) are examples of proteins analyzed for homology.
    • Types of homology include orthologs, which are homologous sequences in different species from a common ancestor, and paralogs, which arise from gene duplication within a species.

    Challenges in Protein Modeling

    • Modeling proteins with sequence identity below 30% poses significant challenges.
    • Enhancements needed include side chain and loop modeling, aiming for improved accuracy and automation in model construction.
    • Existing techniques in comparative modeling are mature but require ongoing improvements for practical applications.

    Automated Homology Modeling Tools

    • SWISS-MODEL: A tool for homology modeling accessible via their website.
    • WHAT IF, CPHModels Server, 3D Jigsaw, SDSC1, and EsyPred3D are additional platforms for automated modeling.

    Protein Threading Technique

    • Protein threading aims to match a target sequence with a native-like fold from the Protein Data Bank (PDB).
    • The energy function used is statistical rather than physics-based, distinguishing between correct and incorrect sequence-structure alignments.

    Crystallography and X-Ray Diffraction

    • Protein crystallography requires well-ordered crystals that strongly diffract X-rays.
    • Cryocooling of crystals to -150°C with cryoprotectants prevents ice formation and extends crystal life during X-ray exposure.
    • Bragg’s Law (2d·sinθ = λ) relates the distance between crystal planes, reflection angle, and wavelength, allowing for unit cell size calculation.

    Challenges in X-Ray Crystallography

    • Growing well-ordered crystals is often difficult due to the nature of globular protein shapes.
    • Diffraction patterns capture specific arrangements of atoms in the crystal, yielding valuable structural information.

    Electron Scattering and Phase Determination

    • Thomson Scattering describes X-ray scattering based on electron density within a crystal.
    • Phase determination is a critical issue in crystallography, resolved mathematically using Fourier transforms.
    • Multiple Isomorphous Replacement (MIR) enhances diffraction patterns through the introduction of heavy atoms to improve phase accuracy while maintaining isomorphous conditions.

    Importance of Amplitude, Phase, and Wavelength

    • Each diffraction spot in experiments is characterized by amplitude (intensity strength), phase (interference relations), and a wavelength defined by the X-ray source.

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    Description

    This quiz covers key concepts in protein homology and modeling, including definitions of homologous proteins, challenges in modeling low identity sequences, and automated tools for homology modeling. Test your knowledge on orthologs, paralogs, and techniques like protein threading.

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