Tutorial 11 - Protein structure, the MODELLER software

A simple, although not always reliable, way to discover the secondary structure of a peptide sequence is to look up a protein with similar primary sequence in a database. Let us try this! The task is to obtain the secondary structure of the following peptide sequence: HYLCKYVINAIPPTLTAKIHFRPELPAERNQLIQRLA

1. Go to https://blast.ncbi.nlm.nih.gov/Blast.cgi and click “Protein blast”.
2. Enter the sequence and enter “Homo sapiens (taxid:9606)” as organism.
3. Click the blast button and wait. This may take up to several minutes.
4. Look for the best matching protein. It should be: “monoamine oxidase A”
5. Enter this protein name to UniProt.
6. Check whether whether the result has a secondary sequence annotation and find the position respective to the BLAST match.

Recall the branch-and-bound threading algorithm from the lecture.

Suppose we have three segments (i, j, k), each of which includes three amino acids. For a given sequence there are three possible starting positions for each segment. (i ∈ {2,3,4}, j ∈ {8,9,10}, k ∈ {13,14,15}) We will be using the simple lower bound:

Suppose that you are given the following values for the scores of the individual segments and the scores for segment interactions:

Using this information, compute the optimal threading.

The purpose of this tutorial is to put our hands on a software for comparative protein structure modelling, namely the MODELLER. We will go through a basic tutorial for this software. At the end this tutorial, you should have a better understanding of what such software is capable of.

Download the MODELLER version for your operating system from: https://salilab.org/modeller/download_installation.html (Note: It is also available from official repositories of some GNU/Linux distributions.)

You need to register yourself in order to obtain a license here: https://salilab.org/modeller/registration.html You should provide your university e-mail in the registration form.

We will follow this tutorial from the MODELLER webpages: https://salilab.org/modeller/tutorial/basic.html.

For those who are interested to learn more about MODELLER, there are also advanced tutorials: https://salilab.org/modeller/tutorial/

If you are interested, you may also have a look at the I-TASSER software.

A tutorial on homology modelling from the university of Frankfurt.

Branch and bound threading example taken from https://www.biostat.wisc.edu/bmi776/lectures/threading.pdf