In-silico molecular designs to treat neurologic and ophthalmologic diseases caused by sorbitol excess: engineering the Agrobacterium vitis protein

BMC Research Notes

Research Note

Joshua Brozek¹  Rahul S. Yerrabelli²  Ashkhan Hojati²  Bhargavee Gnanasambandam²  Shonit Nair Sharma³ 

[1] Carle Foundation Hospital, 61801, Urbana, IL, USA;Carle Illinois College of Medicine, University of Illinois at Urbana-Champaign, 61801, Champaign, IL, USA;Department of Biological Engineering, Massachusetts Institute of Technology, 02139, Cambridge, MA, USA;Brigham and Women’s Hospital, Harvard Medical School, 02115, Boston, MA, USA;Carle Illinois College of Medicine, University of Illinois at Urbana-Champaign, 61801, Champaign, IL, USA;

关键词: Biologic;    Protein Engineering;    PyRosetta;    Cataract;    Neuropathy;   

DOI  :  10.1186/s13104-023-06367-2

 received in 2023-01-11, accepted in 2023-05-23,  发布年份 2023

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s) 2023. corrected publication 2023

【 图 表 】

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