Protein Tertiary Structure

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Questions and Answers

Which level of protein structure is most directly related to the protein's function?

  • Secondary Structure
  • Quaternary Structure
  • Tertiary Structure (correct)
  • Primary Structure

The primary structure of a protein can be easily deduced from its tertiary structure.

False (B)

What is the tertiary structure of a protein?

It is the three-dimensional structure of a protein, formed by the folding and interactions of its secondary structural elements.

In X-ray crystallography, a protein's structure is determined through the analysis of its ______ pattern.

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

Match the following protein structure determination methods with their key characteristic:

<p>X-ray crystallography = Requires protein crystallization Homology modeling = Relies on sequence similarity to known structures Threading = Fits a sequence to a structural fold Ab initio modeling = Predicts structure from scratch without templates</p> Signup and view all the answers

What is the primary advantage of using X-ray crystallography to determine a protein's structure?

<p>It is the most reliable way to determine the tertiary structure of a protein and an academic standard for over 50 years. (C)</p> Signup and view all the answers

Homology modeling can accurately predict protein structure even when there is very low sequence identity between the query sequence and the template.

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

What is the main purpose of homology modeling in protein structure prediction?

<p>To predict the 3D structure of a protein based on its sequence similarity to proteins with known structures.</p> Signup and view all the answers

In homology modeling, the method relies on finding a suitable ______ sequence with a known structure for structure prediction.

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

How does 'threading' or 'fold recognition' differ from homology modeling in protein structure prediction?

<p>Threading is less reliant on sequence identity and more focused on fitting the sequence to a known structural fold or protein fold pattern. (B)</p> Signup and view all the answers

Ab initio protein modeling relies exclusively on experimental data to determine protein structure.

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

What is the role of a 'template library' in the threading method of protein structure prediction?

<p>A template library provides a collection of known protein folds that a query sequence can be aligned to in order to predict its structure.</p> Signup and view all the answers

Unlike homology modeling, ______ modeling techniques predict protein structures from scratch, using physical principles and computational power.

<p>ab initio</p> Signup and view all the answers

Which method is a hierarchical approach to protein structure prediction and structure-based function annotation by using multiple threading approaches?

<p>I-TASSER (B)</p> Signup and view all the answers

Machine learning has no use in protein structure determination.

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

How does machine learning contribute to advancements in protein structure prediction?

<p>Machine learning algorithms identify patterns in protein sequence-structure relationships, enhancing the accuracy and speed of structure prediction.</p> Signup and view all the answers

Machine learning enables computers to learn without being ______ programmed, improving algorithms for protein structure prediction.

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

What is a key outcome of using protein modeling in various scientific applications?

<p>Facilitating computer-aided drug discovery (B)</p> Signup and view all the answers

Protein modeling outputs are exclusively used in academic research and have limited applications in biotechnology or medicine.

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

Give one application of protein modeling in the field of medicine or biotechnology.

<p>Computer-aided drug discovery.</p> Signup and view all the answers

Protein modeling aids drug discovery by allowing researchers to understand how drugs interact with target proteins through molecular ______.

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

Which of the following is a future application of protein modeling?

<p>Creating artificial enzymes (A)</p> Signup and view all the answers

Current protein modeling techniques are sufficient to fully replace traditional experimental methods in all areas of protein research.

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

What is one area of future development for protein modeling in synthetic biology?

<p>In vivo optimization/evolution.</p> Signup and view all the answers

Metagenomic gene mining and synergy with protein engineering approaches represents a big area for future application and development of protein modelling such as ______ evolution.

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

What is indicated by the Nobel Prize received for protein structure prediction?

<p>Recognition of the groundbreaking achievements and impact of protein structure prediction on chemistry, biology, and medicine (A)</p> Signup and view all the answers

The advent of AlphaFold and similar AI models has completely eliminated the need for traditional methods like X-ray crystallography in determining protein structures.

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

Explain how AlphaFold contributes to advances in synthetic biology and the development of artificial enzymes?

<p>AlphaFold's ability to accurately predict protein structures enables the design of novel enzymes with tailored functions and the optimization of synthetic biological systems.</p> Signup and view all the answers

AlphaFold is improving structure prediction accuracy, facilitating design and development of custom ______ enzymes.

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

What is the relationship between a protein's primary structure and its potential conformations?

<p>The primary structure limits and influences, but does not fully determine, the possible conformations. (B)</p> Signup and view all the answers

Flashcards

Primary structure

The linear sequence of amino acids in a protein's chain.

Tertiary structure

The three-dimensional arrangement of atoms in a protein.

X-ray crystallography (Advantages)

A reliable, error-limited method to determine tertiary structure. Has been an academic standard for over 50 years and until recently, the only reliable way to determine tertiary structure of a novel protein.

Types of protein modelling

Homology modelling, threading/fold recognition and ab initio modelling.

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Homology modeling

Constructing a 3D model based on a known structure of a homologous protein.

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Homology modeling: Sequence Identity

Needs minimum 30% amino acid identity, ideally > 50% amino acid identity.

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Threading/fold recognition

An approach that uses the protein fold pattern of a similar protein as the template. Less reliant on sequence identity.

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Ab Initio Modelling

Uses the laws of physics in order to simulate folding of a protein

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Machine learning

A field that enables computers to learn from data without explicit programming.

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Applications of protein modelling

Protein modelling can be used to predict protein interactions, enhance drug discovery, improve QSAR and overcome crystallography limits.

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Future applications for protein modelling

Synthetic biology; in vivo optimisation/evolution, Metagenomic gene mining and synergy with protein engineering approaches, Artificial enzymes (follow on from Alpha Fold).

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Study Notes

Lecture Overview

  • The lecture will cover tertiary structure and its importance, the difference between primary and tertiary structure, X-ray crystallography, the basis for protein modeling, AlphaFold and machine learning approaches, and future benefits.

TDO Components

  • TDO α- and β-components have over 400 amino acids
  • TDO amino acid backbones have bound substrates and secondary structures.
  • Hydrophobic interactions in the active site measure less than 5.0 Ã… (e.g., Van der Waals interactions)
  • 1 angstrom (Ã…) equals 1.0 × 10-10m.
  • Hydrophobic interactions in the active site measure less than 3.8 Ã….

Primary vs. Tertiary Structure

  • Primary structure describes the linear sequence of amino acids in a protein chain and is useful from an evolutionary perspective.
  • Primary structure cannot determine protein function.
  • Tertiary structure is not easily deduced from the primary sequence
  • Tertiary structure reveals more about the protein function
  • Tertiary structure can provide evolutionary insights beyond the primary structure.

X-Ray Crystallography

  • X-ray crystallography helps to determine the protein structure from crystal to a diffraction pattern, then to an electron density map, and finally a protein model.
  • X-ray crystallography is the most reliable, error-limited method for showing tertiary protein structure and has been an academic standard for over 50 years
  • X-ray crystallography was the only reliable method to determine the tertiary structure of a completely novel protein.
  • X-ray crystallography has limitations such as difficulty with proteins like membrane proteins, the need for expertise and equipment, time consumption, expenses and the possibility that a structure solution may fail.

Homology Modeling

  • Homology modeling's minimum amino acid identity is 30% but ideally >50%.

Protein Structure of Proteins

  • Primary protein structure is the sequence of a chain of amino acids.
  • Secondary structure involves local folding of the polypeptide chain into helices or sheets.
  • Tertiary structure is a three-dimensional folding pattern of a protein resulting from side chain interactions.
  • Quaternary structure is a protein consisting of more than one amino acid chain.

Threading

  • Threading uses the fold pattern of a similar protein as the template, not on sequence identity.
  • Prediction via threading involves a protein sequence and a library of core templates, where the return is the best alignment of the sequence to a template.

Protein Modelling

  • Outputs from protein modeling have a variety of applications across a broad range of sciences, including molecular docking, computer-aided drug discovery, and improving QSAR results.
  • It helps to overcome the limitations of protein crystallography and saves especially time and resources.

Machine Learning

  • Machine learning gives computers the ability to learn without being explicitly programmed.

Future Applications

  • Advances in research and biotechnology/medicine are developing the fields of synthetic biology: in vivo optimization/evolution, metagenomic gene mining, synergy with protein engineering approaches such as directed evolution, and creating artificial enzymes.

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