PROT-ON: A structure-based detection of designer PROTein interface MutatiONs
The mutation-induced changes across protein-protein interfaces have often been observed to lead to severe diseases. Therefore, several computational tools have been developed to predict the impact of such mutations. Among these tools, FoldX and EvoEF1 stand out as fast and accurate alternatives. Exp...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1063971/full |
| _version_ | 1811161403885617152 |
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| author | Mehdi Koşaca Mehdi Koşaca İrem Yılmazbilek İrem Yılmazbilek Ezgi Karaca Ezgi Karaca |
| author_facet | Mehdi Koşaca Mehdi Koşaca İrem Yılmazbilek İrem Yılmazbilek Ezgi Karaca Ezgi Karaca |
| author_sort | Mehdi Koşaca |
| collection | DOAJ |
| description | The mutation-induced changes across protein-protein interfaces have often been observed to lead to severe diseases. Therefore, several computational tools have been developed to predict the impact of such mutations. Among these tools, FoldX and EvoEF1 stand out as fast and accurate alternatives. Expanding on the capabilities of these tools, we have developed the PROT-ON (PROTein-protein interface mutatiONs) framework, which aims at delivering the most critical protein interface mutations that can be used to design new protein binders. To realize this aim, PROT-ON takes the 3D coordinates of a protein dimer as an input. Then, it probes all possible interface mutations on the selected protein partner with EvoEF1 or FoldX. The calculated mutational energy landscape is statistically analyzed to find the most enriching and depleting mutations. Afterward, these extreme mutations are filtered out according to stability and optionally according to evolutionary criteria. The final remaining mutation list is presented to the user as the designer mutation set. Together with this set, PROT-ON provides several residue- and energy-based plots, portraying the synthetic energy landscape of the probed mutations. The stand-alone version of PROT-ON is deposited at https://github.com/CSB-KaracaLab/prot-on. The users can also use PROT-ON through our user-friendly web service http://proton.tools.ibg.edu.tr:8001/ (runs with EvoEF1 only). Considering its speed and the range of analysis provided, we believe that PROT-ON presents a promising means to estimate designer mutations. |
| first_indexed | 2024-04-10T06:13:37Z |
| format | Article |
| id | doaj.art-13027dab205646b28f38320135644a3f |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-10T06:13:37Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-13027dab205646b28f38320135644a3f2023-03-02T10:41:17ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-03-011010.3389/fmolb.2023.10639711063971PROT-ON: A structure-based detection of designer PROTein interface MutatiONsMehdi Koşaca0Mehdi Koşaca1İrem Yılmazbilek2İrem Yılmazbilek3Ezgi Karaca4Ezgi Karaca5Izmir Biomedicine and Genome Center, Dokuz Eylul Health Campus, Izmir, TürkiyeIzmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, TürkiyeIzmir Biomedicine and Genome Center, Dokuz Eylul Health Campus, Izmir, TürkiyeMiddle East Technical University, Ankara, TürkiyeIzmir Biomedicine and Genome Center, Dokuz Eylul Health Campus, Izmir, TürkiyeIzmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, TürkiyeThe mutation-induced changes across protein-protein interfaces have often been observed to lead to severe diseases. Therefore, several computational tools have been developed to predict the impact of such mutations. Among these tools, FoldX and EvoEF1 stand out as fast and accurate alternatives. Expanding on the capabilities of these tools, we have developed the PROT-ON (PROTein-protein interface mutatiONs) framework, which aims at delivering the most critical protein interface mutations that can be used to design new protein binders. To realize this aim, PROT-ON takes the 3D coordinates of a protein dimer as an input. Then, it probes all possible interface mutations on the selected protein partner with EvoEF1 or FoldX. The calculated mutational energy landscape is statistically analyzed to find the most enriching and depleting mutations. Afterward, these extreme mutations are filtered out according to stability and optionally according to evolutionary criteria. The final remaining mutation list is presented to the user as the designer mutation set. Together with this set, PROT-ON provides several residue- and energy-based plots, portraying the synthetic energy landscape of the probed mutations. The stand-alone version of PROT-ON is deposited at https://github.com/CSB-KaracaLab/prot-on. The users can also use PROT-ON through our user-friendly web service http://proton.tools.ibg.edu.tr:8001/ (runs with EvoEF1 only). Considering its speed and the range of analysis provided, we believe that PROT-ON presents a promising means to estimate designer mutations.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1063971/fullinterface mutationprotein-protein interactioninterface designEvoEF1FoldX |
| spellingShingle | Mehdi Koşaca Mehdi Koşaca İrem Yılmazbilek İrem Yılmazbilek Ezgi Karaca Ezgi Karaca PROT-ON: A structure-based detection of designer PROTein interface MutatiONs Frontiers in Molecular Biosciences interface mutation protein-protein interaction interface design EvoEF1 FoldX |
| title | PROT-ON: A structure-based detection of designer PROTein interface MutatiONs |
| title_full | PROT-ON: A structure-based detection of designer PROTein interface MutatiONs |
| title_fullStr | PROT-ON: A structure-based detection of designer PROTein interface MutatiONs |
| title_full_unstemmed | PROT-ON: A structure-based detection of designer PROTein interface MutatiONs |
| title_short | PROT-ON: A structure-based detection of designer PROTein interface MutatiONs |
| title_sort | prot on a structure based detection of designer protein interface mutations |
| topic | interface mutation protein-protein interaction interface design EvoEF1 FoldX |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1063971/full |
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