In-silico drug repositioning studies of Candida albicans Nitrogen permease reactivator 1 (Npr1) kinase
Abstract Npr1 is an essential protein in C. albicans, maintains ion homeostasis and nutrient transportation at cell membrane, and regulates the activity of ammonium transporter protein Mep2. Npr1 is one of the nine NPR/HAL family kinases classified under “Other groups” in C. albicans. In this study,...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-08148-2 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849238616206737408 |
|---|---|
| author | Sanjib Das Arka Bagchi Analava Bera Arunima Biswas Analabha Roy Rik Ganguly Amalesh Mondal Deepanjan Chattopadhyay Paromita Saha Mondal Tanushree Mondal Subhasree Samanta Achintya Mohan Goswami Tanima Saha |
| author_facet | Sanjib Das Arka Bagchi Analava Bera Arunima Biswas Analabha Roy Rik Ganguly Amalesh Mondal Deepanjan Chattopadhyay Paromita Saha Mondal Tanushree Mondal Subhasree Samanta Achintya Mohan Goswami Tanima Saha |
| author_sort | Sanjib Das |
| collection | DOAJ |
| description | Abstract Npr1 is an essential protein in C. albicans, maintains ion homeostasis and nutrient transportation at cell membrane, and regulates the activity of ammonium transporter protein Mep2. Npr1 is one of the nine NPR/HAL family kinases classified under “Other groups” in C. albicans. In this study, we had performed protein homology modeling; structure based virtual screening of drugs, docking study and MD simulation. We employed drug repurposing pipeline from which 15 compounds were short listed. Among the compounds, Indacaterol was selected on the basis of high safety profile, binding affinity score value of − 9.3 kcal/mol, as well as its DFG-motif interaction. The best docked pose of the complex was utilized for MD simulation studies. The RMSD values from initial structure and protein–ligand complex were analyzed for the dynamic stability of drug-bound complex and compared with that of the apo-protein. The comparisons of average RMSF values show fluctuation within acceptable range, also very less change of Rg values occur between the protein and protein–ligand throughout the simulation. Further, the complex maintains on an average two hydrogen bonds throughout the simulation period. The binding stability of Npr1 and Indacaterol complex was also verified through Principal Component Analysis. The result secured from these computational approaches and techniques established that the drug has the potential to be developed as an anti-candida lead targeting candidiasis. |
| format | Article |
| id | doaj-art-588aa57d6a69402d8f93d8c76c48bc1a |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-588aa57d6a69402d8f93d8c76c48bc1a2025-08-20T04:01:34ZengNature PortfolioScientific Reports2045-23222025-07-0115111810.1038/s41598-025-08148-2In-silico drug repositioning studies of Candida albicans Nitrogen permease reactivator 1 (Npr1) kinaseSanjib Das0Arka Bagchi1Analava Bera2Arunima Biswas3Analabha Roy4Rik Ganguly5Amalesh Mondal6Deepanjan Chattopadhyay7Paromita Saha Mondal8Tanushree Mondal9Subhasree Samanta10Achintya Mohan Goswami11Tanima Saha12Department of Molecular Biology and Biotechnology, University of KalyaniCell and Molecular Biology Laboratory, Department of Zoology, University of KalyaniCell and Molecular Biology Laboratory, Department of Zoology, University of KalyaniCell and Molecular Biology Laboratory, Department of Zoology, University of KalyaniDepartment of Physics, The University of BurdwanNorth Eastern Hill UniversityDepartment of Molecular Biology and Biotechnology, University of KalyaniDepartment of Molecular Biology and Biotechnology, University of KalyaniDepartment of Molecular Biology and Biotechnology, University of KalyaniDepartment of Molecular Biology and Biotechnology, University of KalyaniDepartment of Molecular Biology and Biotechnology, University of KalyaniDepartment of Physiology, Krishnagar Government CollegeDepartment of Molecular Biology and Biotechnology, University of KalyaniAbstract Npr1 is an essential protein in C. albicans, maintains ion homeostasis and nutrient transportation at cell membrane, and regulates the activity of ammonium transporter protein Mep2. Npr1 is one of the nine NPR/HAL family kinases classified under “Other groups” in C. albicans. In this study, we had performed protein homology modeling; structure based virtual screening of drugs, docking study and MD simulation. We employed drug repurposing pipeline from which 15 compounds were short listed. Among the compounds, Indacaterol was selected on the basis of high safety profile, binding affinity score value of − 9.3 kcal/mol, as well as its DFG-motif interaction. The best docked pose of the complex was utilized for MD simulation studies. The RMSD values from initial structure and protein–ligand complex were analyzed for the dynamic stability of drug-bound complex and compared with that of the apo-protein. The comparisons of average RMSF values show fluctuation within acceptable range, also very less change of Rg values occur between the protein and protein–ligand throughout the simulation. Further, the complex maintains on an average two hydrogen bonds throughout the simulation period. The binding stability of Npr1 and Indacaterol complex was also verified through Principal Component Analysis. The result secured from these computational approaches and techniques established that the drug has the potential to be developed as an anti-candida lead targeting candidiasis.https://doi.org/10.1038/s41598-025-08148-2Candida albicansNitrogen permease reactivator 1IndacaterolDrug-repositioning |
| spellingShingle | Sanjib Das Arka Bagchi Analava Bera Arunima Biswas Analabha Roy Rik Ganguly Amalesh Mondal Deepanjan Chattopadhyay Paromita Saha Mondal Tanushree Mondal Subhasree Samanta Achintya Mohan Goswami Tanima Saha In-silico drug repositioning studies of Candida albicans Nitrogen permease reactivator 1 (Npr1) kinase Scientific Reports Candida albicans Nitrogen permease reactivator 1 Indacaterol Drug-repositioning |
| title | In-silico drug repositioning studies of Candida albicans Nitrogen permease reactivator 1 (Npr1) kinase |
| title_full | In-silico drug repositioning studies of Candida albicans Nitrogen permease reactivator 1 (Npr1) kinase |
| title_fullStr | In-silico drug repositioning studies of Candida albicans Nitrogen permease reactivator 1 (Npr1) kinase |
| title_full_unstemmed | In-silico drug repositioning studies of Candida albicans Nitrogen permease reactivator 1 (Npr1) kinase |
| title_short | In-silico drug repositioning studies of Candida albicans Nitrogen permease reactivator 1 (Npr1) kinase |
| title_sort | in silico drug repositioning studies of candida albicans nitrogen permease reactivator 1 npr1 kinase |
| topic | Candida albicans Nitrogen permease reactivator 1 Indacaterol Drug-repositioning |
| url | https://doi.org/10.1038/s41598-025-08148-2 |
| work_keys_str_mv | AT sanjibdas insilicodrugrepositioningstudiesofcandidaalbicansnitrogenpermeasereactivator1npr1kinase AT arkabagchi insilicodrugrepositioningstudiesofcandidaalbicansnitrogenpermeasereactivator1npr1kinase AT analavabera insilicodrugrepositioningstudiesofcandidaalbicansnitrogenpermeasereactivator1npr1kinase AT arunimabiswas insilicodrugrepositioningstudiesofcandidaalbicansnitrogenpermeasereactivator1npr1kinase AT analabharoy insilicodrugrepositioningstudiesofcandidaalbicansnitrogenpermeasereactivator1npr1kinase AT rikganguly insilicodrugrepositioningstudiesofcandidaalbicansnitrogenpermeasereactivator1npr1kinase AT amaleshmondal insilicodrugrepositioningstudiesofcandidaalbicansnitrogenpermeasereactivator1npr1kinase AT deepanjanchattopadhyay insilicodrugrepositioningstudiesofcandidaalbicansnitrogenpermeasereactivator1npr1kinase AT paromitasahamondal insilicodrugrepositioningstudiesofcandidaalbicansnitrogenpermeasereactivator1npr1kinase AT tanushreemondal insilicodrugrepositioningstudiesofcandidaalbicansnitrogenpermeasereactivator1npr1kinase AT subhasreesamanta insilicodrugrepositioningstudiesofcandidaalbicansnitrogenpermeasereactivator1npr1kinase AT achintyamohangoswami insilicodrugrepositioningstudiesofcandidaalbicansnitrogenpermeasereactivator1npr1kinase AT tanimasaha insilicodrugrepositioningstudiesofcandidaalbicansnitrogenpermeasereactivator1npr1kinase |