Protein structure prediction
using bioinformatic tools
1
Okechukwu Francis
Programme: PhD Biotechnology
SCHOOL OF HEALTH SCIENCE AND TECHNOLOGY (SoHST)

What structure protein structure prediction?
Protein structure prediction refers to the process of predicting the
three-dimensional structure of a protein molecule based on its amino
acid sequence. Proteins are large biomolecules made up of chains of
amino acids that fold into unique three-dimensional shapes, which
determine their functions.
The process of predicting the structure of a protein typically involves
using computational methods to simulate the folding process of the
protein chain, and to predict the interactions between amino acids that
stabilize the final folded structure. These methods can be divided into
two main categories: template-based modelling and ab initio
modelling.

In template-based modelling, the structure of a protein is predicted
based on the known structure of a homologous protein with a similar
amino acid sequence. This method relies on the assumption that
proteins with similar sequences have similar structures.

In ab initio modelling, the structure of a protein is predicted
based on the first principles, without relying on the known
structure of any homologous proteins. This method involves
simulating the folding process of the protein from scratch,
using principles of physics and chemistry to predict the most
stable conformation of the protein.
Protein structure prediction is an important field of study
because it can help to elucidate the functions of proteins, and
can provide insights into the mechanisms of disease and drug
development. However, predicting protein structures is still a
challenging problem, and accurate predictions are not always
possible.

How to analyze protein primary and secondary structure using psi-pred
PSI-PRED is a widely used tool for predicting protein secondary structure from the primary amino acid sequence.
However, it does not analyze the primary structure itself.
To analyze the primary structure of a protein using PSI-PRED, you would first need to use another tool to obtain the
amino acid sequence of the protein of interest. Once you have the sequence, you can use PSI-PRED to predict the
secondary structure, which includes alpha helices, beta sheets, and coil regions.
The predicted secondary structure can then be used to help infer the tertiary structure of the protein.
Here are the basic steps to use PSI-PRED for secondary structure prediction:
1. Obtain the amino acid sequence of the protein of interest.
2. Go to the PSI-PRED website (http://bioinf.cs.ucl.ac.uk/psipred/) and click on the "Submit a Job" button.
3. Paste the amino acid sequence into the text box provided.
4. Choose the "PSI-PRED + PSIPRED-SS2" option for the prediction method.
5. Click the "Submit" button to initiate the prediction.
6. Wait for the prediction to finish, which may take several minutes to a few hours depending on the size of the protein.
7. Download the results, which will include a prediction of the secondary structure in the form of a prediction file.
Once you have the predicted secondary structure, you can use it to help predict the tertiary structure using tools such as
homology modelling or molecular dynamics simulations.

Homology modelling using Swiss model
Homology modelling is a computational method used to predict the three-dimensional structure of a protein based on
the known structure of a related protein. Swiss Model is a widely used tool for homology modelling.
Here are the basic steps to use Swiss Model for homology modelling:
1. Go to the Swiss Model website (https://swissmodel.expasy.org/) and click on the "Start Modeling" button.
2. Paste the amino acid sequence of the protein of interest into the text box provided.
3. Choose a suitable template structure for the homology modelling. Swiss Model provides several options for
selecting a template, including searching the Protein Data Bank (PDB) or using a custom template.
4. Click on the search template to access various templates on the database which would be generated automatically
by Swiss Model.
5. Review the alignment and make any necessary adjustments.
6. Submit the modelling job to Swiss Model.
7. Wait for the modelling to finish, which may take several minutes to a few hours depending on the size of the protein
and the complexity of the modelling.
8. Download the results, which will include the predicted three-dimensional structure of the protein in the form of a
PDB file.
Note: After obtaining the predicted structure, it is important to validate the quality of the model. This can be done
using tools such as PROCHECK or MolProbity, which assess the stereochemical quality of the model and compare it to
known protein structures. Further refinement of the model can also be performed using molecular dynamics simulations
or other methods.

Molecular visualization using jmol
Jmol is a free, open-source software program that is commonly used for molecular visualization and analysis. It
can be used to view and manipulate molecular structures, and to visualize properties such as electrostatic
potential, hydrogen bonding, and solvent accessibility.
Here are the basic steps to use Jmol for molecular visualization:
1. Obtain the molecular structure you wish to visualize in a format that Jmol can read, such as a PDB file.
2. Download and install Jmol on your computer from the Jmol website (http://jmol.sourceforge.net/).
3. Launch Jmol by double-clicking on the Jmol application icon.
4. In the Jmol window, go to the "File" menu and choose "Open".
5. Select the PDB file you wish to visualize and click "Open".
6. The molecule will be displayed in the Jmol window, and you can use the mouse to rotate, zoom, and
translate the view.
7. You can also use Jmol to visualize various molecular properties. For example, to display the electrostatic
potential of the molecule, go to the "Display" menu and choose "Electrostatic Potential". To display
hydrogen bonding, go to the "Display" menu and choose "Hydrogen Bonds".
8. You can also use Jmol to analyze the molecular structure. For example, you can measure distances between
atoms or calculate the surface area of the molecule.
9. When you are finished using Jmol, go to the "File" menu and choose "Exit" to close the program.
Jmol has many other features and capabilities beyond those listed here, so it is recommended to consult the
Jmol user manual or online documentation for more detailed instructions and examples.

Protein structure model evaluation using PROCHECK
PROCHECK is a software program used to evaluate the quality of protein structures. It
assesses the stereochemical quality of the model and compares it to known protein
structures to identify any potential errors or anomalies in the structure.
Here are the basic steps to use PROCHECK for protein structure model evaluation:
 Obtain the protein structure you wish to evaluate in a format that PROCHECK can
read, such as a PDB file.
 Download and install PROCHECK on your computer from the PROCHECK
website (https://www.ebi.ac.uk/thornton-srv/software/PROCHECK/).
 Launch PROCHECK by typing "procheck" at the command prompt or by double-
clicking on the PROCHECK application icon.
 In the PROCHECK window, go to the "File" menu and choose "Load Protein".
 Select the PDB file you wish to evaluate and click "Open".
 The PROCHECK analysis will begin automatically, and the results will be
displayed in the PROCHECK window.

 The PROCHECK results include several types of information, including the
Ramachandran plot, which shows the distribution of the backbone dihedral angles in the
protein structure. PROCHECK compares this distribution to a distribution derived from
high-resolution protein structures to identify any outliers or unusual conformations in the
protein structure. Other information provided by PROCHECK includes the quality factor
(Q-factor), which is a measure of the overall quality of the structure, and a summary of
potential errors or anomalies in the structure.
 Review the PROCHECK results and identify any potential errors or anomalies in the
protein structure. If necessary, refine the structure using additional methods such as
molecular dynamics simulations or energy minimization.
 When you are finished using PROCHECK, go to the "File" menu and choose "Exit" to
close the program.
 PROCHECK has many other features and capabilities beyond those listed here, so it is
recommended to consult the PROCHECK user manual or online documentation for more
detailed instructions and examples.