Molecular Dynamic Simulation and Docking of Cyclophilin A Mutants with its Potential Inhibitors
Background and objectives: Cyclophilin A (CypA) is involved in various human biological processes. Its role in many pathological conditions makes it a promising target for treating human diseases, such as viral infections. The aim of the present study was to investigate docking of CypA mutants with...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Golestan University Of Medical Sciences
2021-04-01
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| Series: | Journal of Clinical and Basic Research |
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| Online Access: | http://jcbr.goums.ac.ir/article-1-316-en.html |
| _version_ | 1797974494067818496 |
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| author | Alireza Mohebbi Azam Mirarab Reyhane Shaddel Mahnaz Shafaei Fallah Ali Memarian |
| author_facet | Alireza Mohebbi Azam Mirarab Reyhane Shaddel Mahnaz Shafaei Fallah Ali Memarian |
| author_sort | Alireza Mohebbi |
| collection | DOAJ |
| description | Background and objectives: Cyclophilin A (CypA) is involved in various human biological processes. Its role in many pathological conditions makes it a promising target for treating human diseases, such as viral infections. The aim of the present study was to investigate docking of CypA mutants with its potential inhibitors using molecular dynamic simulation ((MDS).
Methods: The crystallographic structure of CypA was extracted from the protein database (PDB). Important CypA substitutions were obtained from the literature. CypA inhibitors were taken from chemical databases. The affinity and binding sites of the compounds to CypA and its mutants were also scaled through Autodock Vina. Root-mean-square deviation (RMSD), radios gyration, Lenard-jones potential, and hydrogen bonding were investigated by using MDS for 600 ps.
Results: The findings revealed that SangfA and HBF-0259 had more affinity to the CypA (-7.8Kcal/mol and -7.5Kcal/mol, respectively). Conformational changes were observed in CypA W121A/F mutants. SangfA complexed with CypA and its mutants had relatively stable RMSD. Higher Lenard-Jones potential has been observed in the interaction of SangfA to W121A, HBF-0259 to M61, and SCY-635 to H70F. The SangfA had a higher HBs ratio with CypA.
Conclusion: Given the higher affinity of SangfA and HBF-0259 to CypA and its mutants, they would influence the stability of the protein. RMSD analysis revealed that SangfA is probably ligated to CypA and its mutants, which are relatively stable. Substitution at W121 residue would reduce inhibitor binding to CypA. |
| first_indexed | 2024-04-11T04:20:50Z |
| format | Article |
| id | doaj.art-99ee7a4725594c3ebd53ae2063acb4a5 |
| institution | Directory Open Access Journal |
| issn | 2538-3736 |
| language | English |
| last_indexed | 2024-04-11T04:20:50Z |
| publishDate | 2021-04-01 |
| publisher | Golestan University Of Medical Sciences |
| record_format | Article |
| series | Journal of Clinical and Basic Research |
| spelling | doaj.art-99ee7a4725594c3ebd53ae2063acb4a52022-12-30T17:25:42ZengGolestan University Of Medical SciencesJournal of Clinical and Basic Research2538-37362021-04-01522641Molecular Dynamic Simulation and Docking of Cyclophilin A Mutants with its Potential InhibitorsAlireza Mohebbi0Azam Mirarab1Reyhane Shaddel2Mahnaz Shafaei Fallah3Ali Memarian4 Stem Cell Research Center, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran Department of Microbiology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran Student Research Committee, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran Department of Microbiology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran Background and objectives: Cyclophilin A (CypA) is involved in various human biological processes. Its role in many pathological conditions makes it a promising target for treating human diseases, such as viral infections. The aim of the present study was to investigate docking of CypA mutants with its potential inhibitors using molecular dynamic simulation ((MDS). Methods: The crystallographic structure of CypA was extracted from the protein database (PDB). Important CypA substitutions were obtained from the literature. CypA inhibitors were taken from chemical databases. The affinity and binding sites of the compounds to CypA and its mutants were also scaled through Autodock Vina. Root-mean-square deviation (RMSD), radios gyration, Lenard-jones potential, and hydrogen bonding were investigated by using MDS for 600 ps. Results: The findings revealed that SangfA and HBF-0259 had more affinity to the CypA (-7.8Kcal/mol and -7.5Kcal/mol, respectively). Conformational changes were observed in CypA W121A/F mutants. SangfA complexed with CypA and its mutants had relatively stable RMSD. Higher Lenard-Jones potential has been observed in the interaction of SangfA to W121A, HBF-0259 to M61, and SCY-635 to H70F. The SangfA had a higher HBs ratio with CypA. Conclusion: Given the higher affinity of SangfA and HBF-0259 to CypA and its mutants, they would influence the stability of the protein. RMSD analysis revealed that SangfA is probably ligated to CypA and its mutants, which are relatively stable. Substitution at W121 residue would reduce inhibitor binding to CypA.http://jcbr.goums.ac.ir/article-1-316-en.htmlhbf-0259cyclophilin asanglifehrin acypa inhibitorsmolecular dynamic simulation |
| spellingShingle | Alireza Mohebbi Azam Mirarab Reyhane Shaddel Mahnaz Shafaei Fallah Ali Memarian Molecular Dynamic Simulation and Docking of Cyclophilin A Mutants with its Potential Inhibitors Journal of Clinical and Basic Research hbf-0259 cyclophilin a sanglifehrin a cypa inhibitors molecular dynamic simulation |
| title | Molecular Dynamic Simulation and Docking of Cyclophilin A Mutants with its Potential Inhibitors |
| title_full | Molecular Dynamic Simulation and Docking of Cyclophilin A Mutants with its Potential Inhibitors |
| title_fullStr | Molecular Dynamic Simulation and Docking of Cyclophilin A Mutants with its Potential Inhibitors |
| title_full_unstemmed | Molecular Dynamic Simulation and Docking of Cyclophilin A Mutants with its Potential Inhibitors |
| title_short | Molecular Dynamic Simulation and Docking of Cyclophilin A Mutants with its Potential Inhibitors |
| title_sort | molecular dynamic simulation and docking of cyclophilin a mutants with its potential inhibitors |
| topic | hbf-0259 cyclophilin a sanglifehrin a cypa inhibitors molecular dynamic simulation |
| url | http://jcbr.goums.ac.ir/article-1-316-en.html |
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