In-silico molecular designs to treat neurologic and ophthalmologic diseases caused by sorbitol excess: engineering the Agrobacterium vitis protein
Abstract This work presents the design of a new protein based on the adenosine triphosphate-binding cassette (ABC) transporter solute binding protein (SBP) derived from Agrobacterium vitis, a gram-negative plant pathogen. The Protein Data Bank in Europe’s dictionary of chemical compon...
| Main Authors: | , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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BioMed Central
2023
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| Online Access: | https://hdl.handle.net/1721.1/151042 |
| _version_ | 1826211640831377408 |
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| author | Sharma, Shonit N. Hojati, Ashkhan Gnanasambandam, Bhargavee Yerrabelli, Rahul S. Brozek, Joshua |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Sharma, Shonit N. Hojati, Ashkhan Gnanasambandam, Bhargavee Yerrabelli, Rahul S. Brozek, Joshua |
| author_sort | Sharma, Shonit N. |
| collection | MIT |
| description | Abstract
This work presents the design of a new protein based on the adenosine triphosphate-binding cassette (ABC) transporter solute binding protein (SBP) derived from Agrobacterium vitis, a gram-negative plant pathogen. The Protein Data Bank in Europe’s dictionary of chemical components was utilized to identify sorbitol and D-allitol. Allitol bound to an ABC transporter SBP was identified in the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB). Wizard Pair Fitting and Sculpting tools in PyMOL were used to replace bound allitol with sorbitol. PackMover Python code was used to induce mutations in the ABC transporter SBP’s binding pocket, and changes in free energy for each protein-sorbitol complex were identified. The results indicate that adding charged side chains forms polar bonds with sorbitol in the binding pocket, thus increasing its stabilization. In theory, the novel protein can be used as a molecular sponge to remove sorbitol from tissue and therefore treat conditions affected by sorbitol dehydrogenase deficiency. |
| first_indexed | 2024-09-23T15:09:12Z |
| format | Article |
| id | mit-1721.1/151042 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T15:09:12Z |
| publishDate | 2023 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | mit-1721.1/1510422024-01-05T17:21:00Z In-silico molecular designs to treat neurologic and ophthalmologic diseases caused by sorbitol excess: engineering the Agrobacterium vitis protein Sharma, Shonit N. Hojati, Ashkhan Gnanasambandam, Bhargavee Yerrabelli, Rahul S. Brozek, Joshua Massachusetts Institute of Technology. Department of Biological Engineering Abstract This work presents the design of a new protein based on the adenosine triphosphate-binding cassette (ABC) transporter solute binding protein (SBP) derived from Agrobacterium vitis, a gram-negative plant pathogen. The Protein Data Bank in Europe’s dictionary of chemical components was utilized to identify sorbitol and D-allitol. Allitol bound to an ABC transporter SBP was identified in the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB). Wizard Pair Fitting and Sculpting tools in PyMOL were used to replace bound allitol with sorbitol. PackMover Python code was used to induce mutations in the ABC transporter SBP’s binding pocket, and changes in free energy for each protein-sorbitol complex were identified. The results indicate that adding charged side chains forms polar bonds with sorbitol in the binding pocket, thus increasing its stabilization. In theory, the novel protein can be used as a molecular sponge to remove sorbitol from tissue and therefore treat conditions affected by sorbitol dehydrogenase deficiency. 2023-07-10T11:06:07Z 2023-07-10T11:06:07Z 2023-07-03 2023-07-09T03:17:50Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/151042 BMC Research Notes. 2023 Jul 03;16(1):129 PUBLISHER_CC en https://doi.org/10.1186/s13104-023-06367-2 Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ The Author(s) application/pdf BioMed Central BioMed Central |
| spellingShingle | Sharma, Shonit N. Hojati, Ashkhan Gnanasambandam, Bhargavee Yerrabelli, Rahul S. Brozek, Joshua In-silico molecular designs to treat neurologic and ophthalmologic diseases caused by sorbitol excess: engineering the Agrobacterium vitis protein |
| title | In-silico molecular designs to treat neurologic and ophthalmologic diseases caused by sorbitol excess: engineering the Agrobacterium vitis protein |
| title_full | In-silico molecular designs to treat neurologic and ophthalmologic diseases caused by sorbitol excess: engineering the Agrobacterium vitis protein |
| title_fullStr | In-silico molecular designs to treat neurologic and ophthalmologic diseases caused by sorbitol excess: engineering the Agrobacterium vitis protein |
| title_full_unstemmed | In-silico molecular designs to treat neurologic and ophthalmologic diseases caused by sorbitol excess: engineering the Agrobacterium vitis protein |
| title_short | In-silico molecular designs to treat neurologic and ophthalmologic diseases caused by sorbitol excess: engineering the Agrobacterium vitis protein |
| title_sort | in silico molecular designs to treat neurologic and ophthalmologic diseases caused by sorbitol excess engineering the agrobacterium vitis protein |
| url | https://hdl.handle.net/1721.1/151042 |
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