Protein Function and Gene Ontology
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Questions and Answers

What are the three important features that Gene Ontology captures about function?

  • Molecular Function, Biological Process, Cellular Component (correct)
  • Intrinsic Function, External Factor, Gene Family
  • Molecular Interaction, Biological Pathway, Cellular Environment
  • Enzyme Activity, Cellular Structure, Protein Family
  • Molecular function refers to the broad biological goals achieved by gene products.

    False (B)

    What evidence codes in Gene Ontology signify?

    The reliability and confidence level of the annotations.

    The subcellular structures where a gene product acts are termed __________.

    <p>Cellular Component</p> Signup and view all the answers

    Match the following Gene Ontology terms with their corresponding descriptions:

    <p>Molecular Function = Tasks performed by individual gene products Biological Process = Broad biological goals or objectives Cellular Component = Subcellular structures or locations Evidence Codes = Indicate the reliability of the annotation</p> Signup and view all the answers

    Which sources are considered the most reliable for Gene Ontology annotations?

    <p>Papers and experiments (A)</p> Signup and view all the answers

    RNA-seq can be used to identify whether a set of highly expressed genes belongs to a similar GO term.

    <p>True (A)</p> Signup and view all the answers

    What is the main risk associated with late patenting in drug development?

    <p>Competitors may develop similar drugs (B)</p> Signup and view all the answers

    QSAR stands for Quantitative Structure Activity Relationship.

    <p>True (A)</p> Signup and view all the answers

    What are the three types of modeling in computer-based drug design?

    <ol> <li>Ligands known, receptor unknown; 2. Receptor known, ligands unknown; 3. Receptor-ligand complex known.</li> </ol> Signup and view all the answers

    The first step in ligand screening is to derive a _____.

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

    Match the following docking methods with their descriptions:

    <p>AutoDock Vina = Traditional docking method using simple energy scores GLIDE = Traditional docking method that adjusts ligand conformations DeepDock = Advanced ML method that improves scoring functions DiffDock = Advanced ML method that utilizes diffusive models</p> Signup and view all the answers

    Which database is known for identifying proteins that interact with a query protein?

    <p>STRING (D)</p> Signup and view all the answers

    Prosite motifs are useful for identifying patterns in enzyme active sites.

    <p>True (A)</p> Signup and view all the answers

    What is the main focus of NetGo2.0 in function prediction?

    <p>Machine learning and sequence analysis using k-nearest neighbour.</p> Signup and view all the answers

    The gene ontology prediction challenge is known as _____ which tests function prediction accuracy.

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

    Match the following databases/tools with their primary function:

    <p>STRING = Identifies protein interactions NetGo2.0 = Predicts GO terms using machine learning DALI = Structures alignment and scores Prosite = Identifies enzyme active site patterns</p> Signup and view all the answers

    Which approach integrates multiple sources of information for function prediction?

    <p>Advanced Sequence-Based Approaches (A)</p> Signup and view all the answers

    Structure-based approaches may occasionally reveal relationships that are not discernible by sequence alone.

    <p>True (A)</p> Signup and view all the answers

    What is the main advantage of structure-based approaches in functional annotation?

    <p>Increased confidence due to identification of similar functional residues.</p> Signup and view all the answers

    Pfam uses _____ models to categorize protein domains.

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

    What was the major advancement introduced in NetGo3.0?

    <p>Addition of a protein language model (A)</p> Signup and view all the answers

    Which scale is NOT mentioned for assessing hydrophobicity?

    <p>Mendelian scale (C)</p> Signup and view all the answers

    Signal peptides are typically cleaved off after directing the protein to its cellular location.

    <p>True (A)</p> Signup and view all the answers

    What does DeepTMHMM use to predict transmembrane structures?

    <p>deep learning</p> Signup and view all the answers

    Low complexity regions in protein sequences are often replaced with ______ in BLAST searches.

    <p>lower case letters</p> Signup and view all the answers

    Match the following terms with their descriptions:

    <p>Signal Peptides = Direct proteins to cellular locations Low Complexity Regions = Regions biased toward a few amino acids Coiled-Coils = Intertwined alpha helices Disordered Proteins = Proteins with flexible structural conformations</p> Signup and view all the answers

    What does PONDR-FIT and DISOPRED2 use to predict disorder in proteins?

    <p>Machine learning (D)</p> Signup and view all the answers

    The pLDDT value under 70% indicates a high confidence in AlphaFold predictions.

    <p>False (B)</p> Signup and view all the answers

    What alters the statistical significance scores of sequence alignments?

    <p>Low complexity regions</p> Signup and view all the answers

    DeepTMHMM predicts how the sequence maps from the N- to the _____ terminus.

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

    Regions with low amino acid diversity are informative for protein structure prediction.

    <p>False (B)</p> Signup and view all the answers

    Which of the following statements about fIDPnn is true?

    <p>It has an AUC of 0.814 for predicting disorder. (A)</p> Signup and view all the answers

    DisProt is considered the gold standard database for intrinsically disordered proteins.

    <p>True (A)</p> Signup and view all the answers

    What is the purpose of Clinical Phase I in drug development?

    <p>Determine a safe dosage and assess side effects.</p> Signup and view all the answers

    A __________ is a chemically optimized version of a hit designed to enhance therapeutic efficacy.

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

    Match the clinical development phases with their primary focus:

    <p>Phase I = Determine safe dosage and side effects Phase II = Refine side effects and initial effectiveness Phase III = Prove effectiveness and evaluate safety Phase IV = Post-marketing surveillance</p> Signup and view all the answers

    What does the term 'Hit' refer to in drug discovery?

    <p>A small molecule identified with the desired therapeutic effect (D)</p> Signup and view all the answers

    Participants in Clinical Phase III trials are usually healthy volunteers.

    <p>False (B)</p> Signup and view all the answers

    What is the goal of the Regulatory Phase in drug development?

    <p>Obtain approval for the drug’s use and marketing.</p> Signup and view all the answers

    The database that correlates strongly with disorder predictions from AlphaFold2 pLDDT is called __________.

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

    What are the common functions annotated in fIDPnn predictions?

    <p>DNA-binding, RNA-binding, Protein-binding, Linkers (D)</p> Signup and view all the answers

    Flashcards

    Gene Ontology (GO)

    A controlled vocabulary system used to describe the functions of genes and gene products (proteins and RNA) across all organisms.

    Molecular Function

    The specific tasks performed by individual gene products, like binding to a molecule or catalyzing a reaction.

    Biological Process

    The overall biological objective or goal that a gene product contributes to, such as cell division or metabolism.

    Cellular Component

    The location within a cell where a gene product is active, like a specific organelle or complex.

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    Evidence Code

    An annotation that indicates the source of information used to assign a GO term, helping to assess its reliability.

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    Function Prediction

    Using existing knowledge about protein homology and families to predict the function of new or uncharacterized proteins.

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    GO Term Clustering

    The process of grouping related GO terms to gain a broader understanding of the integrated functions of a set of proteins.

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    Specific Domain Libraries

    Specialized databases containing curated information on protein domains, motifs, and profiles, aiding in functional annotation.

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    Prosite Motifs

    A collection of short patterns that can be used to identify specific functional sites in proteins, such as active enzyme sites.

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    Prosite Profiles

    More extensive profiles than motifs, encompassing larger sequence patterns that pinpoint specific functions, such as carrier proteins.

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    Interactome Databases

    Databases that analyze protein-protein interactions, helping to infer function based on the principle that interacting proteins often have similar functions.

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    STRING Database

    A database that uses diverse sources of information, including curated interactions and predictions from various bioinformatics methods, to identify proteins interacting with a query protein.

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    NetGo2.0

    A machine learning approach that integrates multiple data sources, such as BLAST results, InterPro features, amino acid frequencies, and STRING network information, to predict protein function.

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    Structure-Based Approach

    A method for functional prediction based on the similarity of 3D structures, assuming that proteins with similar structures often have similar functions.

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    Structural Search

    A database search tool that compares the 3D structure of a query protein to a database of known structures, providing a score for similarity.

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    Similar Fold Search

    A type of structural searching that focuses on identifying proteins with similar folds, suggesting potential functional relationships.

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    QSAR

    A mathematical relationship that connects the activity of a molecule to its structure.

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    Redocking

    A method that tests the ability of a docking algorithm to predict the correct pose of a ligand within a protein, by using the known structure of a protein-ligand complex.

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    Lock-and-key approach

    An approach where the ligand's conformation is adjusted while keeping the protein structure mostly rigid, allowing only side-chain adjustments.

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    Training on one protein, testing on a homologous protein

    An evaluation method where a docking algorithm is trained on one protein and then tested on a homologous protein.

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    DiffDock

    It uses diffusion models to search and score ligands. It works by taking known complexes, adding noise, and then removing the noise.

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    Signal Peptide

    A sequence of amino acids at the beginning of a protein that directs it to the correct location within the cell and is often removed after transport.

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    Hydrophobic Plot

    A method for predicting transmembrane regions within a protein sequence by analyzing the hydrophobicity of amino acids.

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    Low Complexity Region

    A region in a protein sequence with a high concentration of a few specific amino acids, making it difficult to align with other sequences.

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    Coiled-Coil

    Two or three alpha helices intertwined, forming a structural motif in proteins.

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    Disordered Protein

    A protein that lacks a defined three-dimensional structure and is highly flexible, often involved in protein recognition.

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    Disordered Regions

    Regions within a protein that lack a defined structure and are often found at the ends of the protein or as loops.

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    DeepTMHMM

    A deep learning algorithm designed to accurately predict both transmembrane structures and signal peptides in protein sequences.

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    SEG Program

    A program used to identify low complexity regions in protein sequences and replace them with lowercase letters in BLAST searches.

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    COILS

    A technique used to identify coiled-coil structures in proteins.

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    PONDR-FIT and DISOPRED2

    A program that predicts disordered regions in protein sequences based on machine learning.

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    Target

    A protein or molecule whose activity is modified to achieve therapeutic effects.

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    Hit

    A small molecule identified through biological or computational screening with the desired effect (typically IC50 ≤ 1 µM).

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    Lead

    A chemically optimized version of a hit, designed to enhance therapeutic efficacy and minimize adverse effects.

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    IC50

    A measure of how much of a drug is needed to achieve a desired effect.

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    Clinical Phase I

    The first phase of clinical trials, involving a small group of individuals to determine a safe dosage and assess side effects.

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    Clinical Phase II

    The second phase of clinical trials, focusing on refining results from Phase I and determining initial effectiveness.

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    Clinical Phase III

    The third phase of clinical trials, involving a large group of patients to definitively prove effectiveness and further evaluate safety.

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    Regulatory Phase

    The process of submitting data to regulatory agencies for approval of drug use and marketing.

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    Sales and Monitoring Phase (Phase IV)

    The post-marketing surveillance phase, monitoring long-term safety and effectiveness of a drug.

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    DisProt

    A database of curated information about intrinsically disordered proteins and regions, providing valuable insights into their functions.

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    Study Notes

    Protein Function and Gene Ontology

    • Gene ontology (GO) classifies gene products (proteins and RNA) based on their functions.
    • GO provides a controlled vocabulary applicable to all organisms, documenting functions beyond what enzyme classification systems offer.
    • GO captures three key functional aspects: molecular function, biological process, and cellular component.
    • Molecular function defines the tasks performed by a gene product (e.g., GTPase activity).
    • Biological process outlines the broader biological goals fulfilled by the gene product (e.g., mitosis).
    • Cellular component describes the location or active location of a gene product (e.g., nucleus).
    • Evidence codes (e.g., experimental or computational analysis) associated with annotations indicate their reliability.

    Function Prediction Approaches

    • Protein function prediction uses homology and protein families.
    • General homology searches (using BLAST, PSIBLAST, HMMs) compare a query sequence to a database to identify similar sequences.
    • Orthologs share function and high sequence identity (often >85%) across species.
    • Paralogs, arising from gene duplication, have related but not identical functions within a species, exhibiting lower sequence identity than orthologs.

    Homology-Based Predictions and Domain Libraries

    • Homology searches identify local similarities (shared domains) between sequences.
    • Domains with similar structures may share function, even if the overall protein functions differ.
    • Specific Domain Libraries: like InterPro, Prosite, Pfam are used to search for function based on specific motifs/patterns not just overall sequence similarity.

    Structure-Based Predictions

    • Matching 3D structures (superposition/alignment).
    • Comparing functional residues to imply function transfer
    • Structural searching helps find similar folds (using tools like DALI, CATH, and Foldseek to determine similar 3D structures).

    Advanced Sequence-Based Approaches

    • Different prediction approaches combine data sources to make predictions based on interactions or related functions in databases.
    • STRING Database: used to identify proteins that interact with a query proteins
    • NetGo: machine learning approach
    • Combining multiple data sources often improves predictive accuracy and provides a more holistic view.

    Transmembrane Region Prediction

    • Early methods to predict transmembrane regions: relied on hydrophobic residue runs.
    • More advanced methods: utilize hydrophobicity scales, and often combine these methods with machine learning.

    Prediction of Disorder

    • Some proteins contain unstructured or disordered regions not well represented by typical 3D structures.
    • Deep learning algorithms (e.g., DISOPRED2, PONDR-FIT, pIDPnn) are now used to predict disordered regions and functions like binding activities.
    • DisProt is a valuable database for intrinsically disordered proteins and regions.

    Drug Discovery Pipeline

    • Target: A protein or molecule whose activity is modified to achieve therapeutic effects.
    • Hit: A compound with a desirable effect (like IC50 ≤ 1 µM).
    • Lead: Modified hits to optimize efficacy, reduce toxicity.
    • Clinical trials (Phase I-III) evaluate safety, efficacy, and dosage.
    • Regulatory approval & sales/monitoring phase follow clinical trials.

    Computer-Based Drug Design

    • Ligand Screening: Use Quantitative Structure-Activity Relationships (QSAR) and virtual screening to identify potential drug candidates through docking to target protein.
    • Docking Methods: Traditional methods use atom-atom interactions to score docking outcomes; advanced methods (like deep learning) offer improved accuracy and incorporate better modeling of conformational changes.

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    Description

    Explore the classification of gene products based on their functions through Gene Ontology (GO). This quiz covers key aspects such as molecular function, biological processes, and the cellular components involved in protein function prediction. Test your knowledge on how these concepts apply to various biological systems.

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