Protein Structure and Homology Modelling

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Questions and Answers

What percentage of sequences have more than 25% identity with a known structure in the PDB?

35%

10%

20%

28% (correct)

What is the general guideline for sequence identity in template-based modeling?

> 50%

> 70%

> 30% (correct)

> 20%

What database is commonly used for searching for proteins with known structures?

UniProt

GenBank

PDB (correct)

SCOP

What is the name of the algorithm used to search for proteins with known structures?

BLAST Signup and view all the answers

What is the purpose of multiple sequence alignment in template-based modeling?

To predict conserved regions Signup and view all the answers

What is the term for the process of constructing a protein model from a template?

Model construction Signup and view all the answers

What is the name of the software used for model construction?

Swissmodel Signup and view all the answers

What is the purpose of identifying conserved functional residues in the alignment?

To improve the accuracy of the model Signup and view all the answers

What is the main goal of energy minimization in protein simulations?

To find a set of coordinates representing the minimum energy conformation Signup and view all the answers

Which of the following is a characteristic of Quantic Methods (QM)?

It takes electronic orbitals into account Signup and view all the answers

What is the main limitation of Molecular Mechanics (MM) force fields?

They cannot escape the local minimum close to the starting structure Signup and view all the answers

What is the main goal of homology modeling?

To identify a protein of known structure Signup and view all the answers

What is the purpose of simulated annealing in protein simulations?

To allow the energy function to increase momentarily to cross energy barriers Signup and view all the answers

What is the main difference between ab initio and homology modeling?

Ab initio modeling builds 3D models based on the sequence, while homology modeling uses a template Signup and view all the answers

What is the main purpose of loop modeling?

To model loops of unknown structure Signup and view all the answers

What is the main advantage of Hybrid QM/MM methods?

They can be applied to part of a molecule, such as the active site Signup and view all the answers

What is the input required for the Modeller software?

Target sequence, template structures, and alignment Signup and view all the answers

What is the main goal of fold recognition or threading?

To determine the fold of a protein Signup and view all the answers

What is the purpose of energy minimization in protein modeling?

To estimate the internal energy of a protein Signup and view all the answers

What is the purpose of stereochemical corrections?

To suppress steric hindrance Signup and view all the answers

What is the purpose of native conformation in protein modeling?

To find the minimum free energy conformation Signup and view all the answers

What is the purpose of the probability density function (pdf) in protein modeling?

To represent spatial constraints Signup and view all the answers

What is the purpose of alignment in protein modeling?

To generate spatial constraints Signup and view all the answers

What are the secondary structure predictions based on?

Multiple sequence alignment Signup and view all the answers

What is the sequence length of the provided protein?

372 Signup and view all the answers

What percentage of the protein sequence is predicted to be an alpha helix?

35.48% Signup and view all the answers

Which of the following methods predicts a 310 helix?

DPM Signup and view all the answers

What is the purpose of the Ramachandran Plot?

To check the stereochemistry of a protein Signup and view all the answers

What is the name of the website where the protein model was built?

SwissModel.expasy.org Signup and view all the answers

What is the percentage of the protein sequence predicted to be a random coil?

21.24% Signup and view all the answers

What is the main goal of virtual screening?

To score, rank or filter a set of chemical structures using computational procedures Signup and view all the answers

What is the purpose of a search algorithm in docking software?

To generate a large number of poses of a molecule in the binding site Signup and view all the answers

Why might water molecules be removed from a PDB structure?

Except where it is known that they play an important role in coordinating to the ligand Signup and view all the answers

What is the purpose of a scoring function in docking software?

To calculate a score or binding affinity for a particular pose Signup and view all the answers

What is protein-ligand docking not to be confused with?

Protein-protein docking Signup and view all the answers

What is the outcome of docking?

Both a and b Signup and view all the answers

Why might explicit hydrogens be added to a protein structure?

Because many docking programs require the protein to have explicit hydrogens Signup and view all the answers

What is the purpose of virtual screening in the context of experimental design?

To help decide which compounds to screen experimentally Signup and view all the answers

Study Notes

Homology Modeling and Protein Structure

Homology modeling is a method used to predict the 3D structure of a protein based on its sequence similarity to a protein of known structure
The process involves identifying a protein of known structure (template) that shares a high sequence identity with the target protein
The sequence identity between the target protein and the template should be above 30% for reliable modeling

Energy Minimization and Molecular Dynamics

Energy minimization is a method used to find the most stable conformation of a protein
Molecular mechanics (MM) force fields are used to simulate protein dynamics and calculate the energy of the system
The energetic state of a protein is a function of its atomic coordinates, and energy minimization algorithms (e.g. steepest descent, conjugate gradient, and Newton-Raphson) are used to find the minimum energy conformation
Molecular dynamics (MD) simulations are used to study the dynamics of protein systems, but may get stuck in local energy minima

Quantum Mechanics and Hybrid Methods

Quantum mechanics (QM) methods are used to study the electronic structure of molecules and are more accurate but computationally expensive
Hybrid QM/MM methods are used to study the active site of a protein, combining the accuracy of QM with the efficiency of MM methods

Homology Modeling Steps

Search for homologous sequences in databases (e.g. GenBank, UniProt, PIR) using algorithms such as FASTA and BLAST
Perform multiple sequence alignment to identify conserved regions and predict the fold of the protein
Build a core model using the template structure and align the target sequence to the template
Loop modeling involves searching for homologous fragments in databases and reconstructing the loop using energy minimization and MD simulations
Side chain modeling involves choosing stable rotamers based on the template structure and stereochemistry

Model Evaluation and Verification

The quality of the model can be evaluated using various metrics, including stereochemistry, bond lengths, and angles
The model can be optimized using energy minimization and MD simulations
Verification involves checking the model against experimental data and assessing its functional properties

Virtual Screening and Docking

Virtual screening is a computational method used to identify potential ligands that bind to a protein
Docking software consists of a search algorithm and a scoring function to predict the binding affinity of a ligand
Popular docking software includes AutoDock, DOCK, and Glide, among others

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Description

This quiz covers the basics of protein structure, homology modelling, and protein-ligand interactions. It also touches on molecular mechanics force fields and the Protein Data Bank.