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Fast method to find sterically possible amino acid substitutions

Čalyševa, Jelena (2016) BINP30 20161
Degree Projects in Bioinformatics
Abstract (Swedish)
With the growing pool of deposited protein structures, the need for structural analysis tools grows. In study of amino acid substitutions the variety of analysis tools is high; nevertheless, there is a lack of programs serving specific purpose, such as identifying if an amino acid substitution would cause a clash in the structure or not, given just the structure of the original protein. In this study, such tool has been developed and proven to be fast and reasonably effective.
Popular Abstract
Analysing structural damage caused by changes in proteins

In an organism, even only one single change of an amino acid can sometimes lead to disease, if the protein is a part of an important biological function. Because of that, it is important to study those changes and be able to predict if an amino acid substitution would cause harm. There are various ways a substitution can be harmful to a protein, one of them being the effect on its 3D structure. If the new amino acid is bigger or otherwise more spacious than the one that was substituted, atoms of the new amino acid can clash with other atoms in the structure and cause structural damage. Because of that, clinical research is in need of methods to identify if an amino acid... (More)
Analysing structural damage caused by changes in proteins

In an organism, even only one single change of an amino acid can sometimes lead to disease, if the protein is a part of an important biological function. Because of that, it is important to study those changes and be able to predict if an amino acid substitution would cause harm. There are various ways a substitution can be harmful to a protein, one of them being the effect on its 3D structure. If the new amino acid is bigger or otherwise more spacious than the one that was substituted, atoms of the new amino acid can clash with other atoms in the structure and cause structural damage. Because of that, clinical research is in need of methods to identify if an amino acid substitution would cause clashes in protein structure or not.

In this project, a computer program was developed to identify if amino acid substitution would cause clashes in protein structure or not. The program takes a file with 3D coordinates of a protein as an input. There is also an option to specify which amino acids should be substituted with which; otherwise, all amino acids in the protein are checked for all possible substitutions. The program gives an output of a table of substitutions and identification on whether they would cause clashes or not. Also, an option of getting the coordinates of the newly substituted amino acid exists.

To achieve this goal, Python programming was used, with implementation of various algorithms to organize the coordinates and perform the calculations. The substituted amino acids were modeled into the structure and clashes between atoms were simply identified by calculating if the distance between the new atoms of the new substituted amino acid and already existing atoms is above or under a certain threshold. The program turned out to be fast and effective, while testing it on various datasets of protein structures.

This kind of a program can be used widely in research and clinical analysis to study known and unknown variations in proteins, to model new proteins and to perform other kind of analysis of amino acid substitutions in proteins.




Supervisor: Mauno Vihinen
Master degree project 30 credits in Bioinformatics 2016
Department of Experimental Medical Science, BMC, Lund University (Less)
Please use this url to cite or link to this publication:
author
Čalyševa, Jelena
supervisor
organization
course
BINP30 20161
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
8891866
date added to LUP
2016-09-15 15:39:37
date last changed
2016-09-15 15:39:37
@misc{8891866,
  abstract     = {With the growing pool of deposited protein structures, the need for structural analysis tools grows. In study of amino acid substitutions the variety of analysis tools is high; nevertheless, there is a lack of programs serving specific purpose, such as identifying if an amino acid substitution would cause a clash in the structure or not, given just the structure of the original protein. In this study, such tool has been developed and proven to be fast and reasonably effective.},
  author       = {Čalyševa, Jelena},
  language     = {eng},
  note         = {Student Paper},
  title        = {Fast method to find sterically possible amino acid substitutions},
  year         = {2016},
}