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PON-SC - program for identifying steric clashes caused by amino acid substitutions

Čalyševa, Jelena and Vihinen, Mauno LU (2017) In BMC Bioinformatics 18(1).
Abstract

Background: Amino acid substitutions due to DNA nucleotide replacements are frequently disease-causing because of affecting functionally important sites. If the substituting amino acid does not fit into the protein, it causes structural alterations that are often harmful. Clashes of amino acids cause local or global structural changes. Testing structural compatibility of variations has been difficult due to the lack of a dedicated method that could handle vast amounts of variation data produced by next generation sequencing technologies. Results: We developed a method, PON-SC, for detecting protein structural clashes due to amino acid substitutions. The method utilizes side chain rotamer library and tests whether any of the common... (More)

Background: Amino acid substitutions due to DNA nucleotide replacements are frequently disease-causing because of affecting functionally important sites. If the substituting amino acid does not fit into the protein, it causes structural alterations that are often harmful. Clashes of amino acids cause local or global structural changes. Testing structural compatibility of variations has been difficult due to the lack of a dedicated method that could handle vast amounts of variation data produced by next generation sequencing technologies. Results: We developed a method, PON-SC, for detecting protein structural clashes due to amino acid substitutions. The method utilizes side chain rotamer library and tests whether any of the common rotamers can be fitted into the protein structure. The tool was tested both with variants that cause and do not cause clashes and found to have accuracy of 0.71 over five test datasets. Conclusions: We developed a fast method for residue side chain clash detection. The method provides in addition to the prediction also visualization of the variant in three dimensional structure.

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Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Amino acid substitution, Side chain rotamers, Structural clashes, Variation interpretation
in
BMC Bioinformatics
volume
18
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85035324731
  • wos:000416903700005
ISSN
1471-2105
DOI
10.1186/s12859-017-1947-7
language
English
LU publication?
yes
id
481e8a00-726f-42db-a868-f52e12429253
date added to LUP
2017-12-12 12:27:01
date last changed
2018-01-16 13:27:40
@article{481e8a00-726f-42db-a868-f52e12429253,
  abstract     = {<p>Background: Amino acid substitutions due to DNA nucleotide replacements are frequently disease-causing because of affecting functionally important sites. If the substituting amino acid does not fit into the protein, it causes structural alterations that are often harmful. Clashes of amino acids cause local or global structural changes. Testing structural compatibility of variations has been difficult due to the lack of a dedicated method that could handle vast amounts of variation data produced by next generation sequencing technologies. Results: We developed a method, PON-SC, for detecting protein structural clashes due to amino acid substitutions. The method utilizes side chain rotamer library and tests whether any of the common rotamers can be fitted into the protein structure. The tool was tested both with variants that cause and do not cause clashes and found to have accuracy of 0.71 over five test datasets. Conclusions: We developed a fast method for residue side chain clash detection. The method provides in addition to the prediction also visualization of the variant in three dimensional structure.</p>},
  articleno    = {531},
  author       = {Čalyševa, Jelena and Vihinen, Mauno},
  issn         = {1471-2105},
  keyword      = {Amino acid substitution,Side chain rotamers,Structural clashes,Variation interpretation},
  language     = {eng},
  month        = {11},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {BMC Bioinformatics},
  title        = {PON-SC - program for identifying steric clashes caused by amino acid substitutions},
  url          = {http://dx.doi.org/10.1186/s12859-017-1947-7},
  volume       = {18},
  year         = {2017},
}