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BMC Bioinformatics. 2017 Nov 29;18(1):531. doi: 10.1186/s12859-017-1947-7.

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

Author information

1
Protein Structure and Bioinformatics, Department of Experimental Medical Science, Lund University, BMC B13, SE-22 184, Lund, Sweden.
2
Present address: EMBL Heidelberg, Meyerhofstraße 1, 69117, Heidelberg, Germany.
3
Protein Structure and Bioinformatics, Department of Experimental Medical Science, Lund University, BMC B13, SE-22 184, Lund, Sweden. mauno.vihinen@med.lu.se.

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 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.

KEYWORDS:

Amino acid substitution; Side chain rotamers; Structural clashes; Variation interpretation

PMID:
29187139
PMCID:
PMC5707825
DOI:
10.1186/s12859-017-1947-7
[Indexed for MEDLINE]
Free PMC Article

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