PON-SC – program for identifying steric clashes caused by amino acid substitutions
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 ac...
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| Format: | Article |
| Language: | English |
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BMC
2017-11-01
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| Series: | BMC Bioinformatics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12859-017-1947-7 |
| _version_ | 1811282633548627968 |
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| author | Jelena Čalyševa Mauno Vihinen |
| author_facet | Jelena Čalyševa Mauno Vihinen |
| author_sort | Jelena Čalyševa |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T01:54:53Z |
| format | Article |
| id | doaj.art-53cff3355a1947788524ca9f233d6b1a |
| institution | Directory Open Access Journal |
| issn | 1471-2105 |
| language | English |
| last_indexed | 2024-04-13T01:54:53Z |
| publishDate | 2017-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Bioinformatics |
| spelling | doaj.art-53cff3355a1947788524ca9f233d6b1a2022-12-22T03:07:46ZengBMCBMC Bioinformatics1471-21052017-11-011811810.1186/s12859-017-1947-7PON-SC – program for identifying steric clashes caused by amino acid substitutionsJelena Čalyševa0Mauno Vihinen1Protein Structure and Bioinformatics, Department of Experimental Medical Science, Lund UniversityProtein Structure and Bioinformatics, Department of Experimental Medical Science, Lund UniversityAbstract 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.http://link.springer.com/article/10.1186/s12859-017-1947-7Amino acid substitutionVariation interpretationStructural clashesSide chain rotamers |
| spellingShingle | Jelena Čalyševa Mauno Vihinen PON-SC – program for identifying steric clashes caused by amino acid substitutions BMC Bioinformatics Amino acid substitution Variation interpretation Structural clashes Side chain rotamers |
| title | PON-SC – program for identifying steric clashes caused by amino acid substitutions |
| title_full | PON-SC – program for identifying steric clashes caused by amino acid substitutions |
| title_fullStr | PON-SC – program for identifying steric clashes caused by amino acid substitutions |
| title_full_unstemmed | PON-SC – program for identifying steric clashes caused by amino acid substitutions |
| title_short | PON-SC – program for identifying steric clashes caused by amino acid substitutions |
| title_sort | pon sc program for identifying steric clashes caused by amino acid substitutions |
| topic | Amino acid substitution Variation interpretation Structural clashes Side chain rotamers |
| url | http://link.springer.com/article/10.1186/s12859-017-1947-7 |
| work_keys_str_mv | AT jelenacalyseva ponscprogramforidentifyingstericclashescausedbyaminoacidsubstitutions AT maunovihinen ponscprogramforidentifyingstericclashescausedbyaminoacidsubstitutions |