Unveiling the molecular activity of HIV towards the CD4: A study based on subtype C via docking and dynamics approach
Background: Acquired Immunodeficiency Syndrome (AIDS) is a critical global health issue caused by the human immunodeficiency virus (HIV). It has different strains and subtypes; among these, Subtype C accounts for higher infection rates than others. Despite its high prevalence, the molecular interact...
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Elsevier
2025-03-01
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| Series: | Journal of Genetic Engineering and Biotechnology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1687157X25000010 |
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| author | Saurav Kumar Mishra Neeraj Kumar Zsolt Tóth Yousef A. Bin Jardan Shopnil Akash John J. Georrge |
| author_facet | Saurav Kumar Mishra Neeraj Kumar Zsolt Tóth Yousef A. Bin Jardan Shopnil Akash John J. Georrge |
| author_sort | Saurav Kumar Mishra |
| collection | DOAJ |
| description | Background: Acquired Immunodeficiency Syndrome (AIDS) is a critical global health issue caused by the human immunodeficiency virus (HIV). It has different strains and subtypes; among these, Subtype C accounts for higher infection rates than others. Despite its high prevalence, the molecular interactions with host receptors, specifically CD4, have not yet been explored. Methods: This study investigates the molecular interactions between HIV subtype C and the CD4 receptor via docking and dynamics approach. Four HIV targets were examined, and their structure was modelled. Subsequently, these models were docked with the CD4 to analyze their binding interaction. The stability was examined over 200 simulations via Desmond software, and trajectories were analyzed, followed by Root mean square deviation (RMSD), root mean square fluctuation (RMSF), and the radius of gyration (Rg), PCA (principal component analysis), etc., to assess their stability and interaction dynamics. Results: The four target structures were modelled, and their quality was validated. Further, the docking analysis with CD4 revealed that the Envelope glycoprotein has −13.6 kcal/mol, protease has −11.2 kcal/mol, Reverse transcriptase has −12.4 kcal/mol, and integrase has −13.1 kcal/mol binding affinity towards it, followed by the number of hydrogen bond, such as 9, 6, 11, 6. The simulation over 200 ns demonstrated that the average RMSD for each complex started stabilizing within the 0.9 Å − 3.4 Å, followed by 25–50 ns, whereas the RMSF, Rg and PCA revealed the relative compactness and flexibility varied across different viral targets. Conclusions: The study successfully identified the interactive residues of HIV subtype C toward the CD4 receptor. The binding affinities and stability data provide valuable insights into Subtype C’s molecular interactions with the host, and these findings underscore the potential for developing treatments that disrupt these interactions to combat HIV more effectively. |
| format | Article |
| id | doaj-art-e731e8bc721d4ca2bf51126a2957d3c0 |
| institution | OA Journals |
| issn | 1687-157X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
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| series | Journal of Genetic Engineering and Biotechnology |
| spelling | doaj-art-e731e8bc721d4ca2bf51126a2957d3c02025-08-20T01:58:27ZengElsevierJournal of Genetic Engineering and Biotechnology1687-157X2025-03-0123110045710.1016/j.jgeb.2025.100457Unveiling the molecular activity of HIV towards the CD4: A study based on subtype C via docking and dynamics approachSaurav Kumar Mishra0Neeraj Kumar1Zsolt Tóth2Yousef A. Bin Jardan3Shopnil Akash4John J. Georrge5Department of Bioinformatics, University of North Bengal, District-Darjeeling, West Bengal 734013, IndiaDepartment of Pharmaceutical Chemistry Bhupal Nobles, College of Pharmacy, Udaipur, Rajasthan 313001, IndiaFaculty of Wood Engineering and Creative Industries, University of Sopron, Bajcsy-Zs. u. 4, Sopron, Hungary; Corresponding author at: Faculty of Wood Engineering and Creative Industries, University of Sopron, Hungary.Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 11451, Riyadh, Saudi ArabiaComputational Biology research laboratory, Department of Pharmacy, Daffodil International University, Birulia 1216, Ashulia, Dhaka, BangladeshDepartment of Bioinformatics, University of North Bengal, District-Darjeeling, West Bengal 734013, India; Corresponding author at: Department of Bioinformatics, University of North Bengal, District-Darjeeling, West Bengal 734013, India.Background: Acquired Immunodeficiency Syndrome (AIDS) is a critical global health issue caused by the human immunodeficiency virus (HIV). It has different strains and subtypes; among these, Subtype C accounts for higher infection rates than others. Despite its high prevalence, the molecular interactions with host receptors, specifically CD4, have not yet been explored. Methods: This study investigates the molecular interactions between HIV subtype C and the CD4 receptor via docking and dynamics approach. Four HIV targets were examined, and their structure was modelled. Subsequently, these models were docked with the CD4 to analyze their binding interaction. The stability was examined over 200 simulations via Desmond software, and trajectories were analyzed, followed by Root mean square deviation (RMSD), root mean square fluctuation (RMSF), and the radius of gyration (Rg), PCA (principal component analysis), etc., to assess their stability and interaction dynamics. Results: The four target structures were modelled, and their quality was validated. Further, the docking analysis with CD4 revealed that the Envelope glycoprotein has −13.6 kcal/mol, protease has −11.2 kcal/mol, Reverse transcriptase has −12.4 kcal/mol, and integrase has −13.1 kcal/mol binding affinity towards it, followed by the number of hydrogen bond, such as 9, 6, 11, 6. The simulation over 200 ns demonstrated that the average RMSD for each complex started stabilizing within the 0.9 Å − 3.4 Å, followed by 25–50 ns, whereas the RMSF, Rg and PCA revealed the relative compactness and flexibility varied across different viral targets. Conclusions: The study successfully identified the interactive residues of HIV subtype C toward the CD4 receptor. The binding affinities and stability data provide valuable insights into Subtype C’s molecular interactions with the host, and these findings underscore the potential for developing treatments that disrupt these interactions to combat HIV more effectively.http://www.sciencedirect.com/science/article/pii/S1687157X25000010HIV subtype CCD4 receptorDockingPCAMolecular dynamics simulation |
| spellingShingle | Saurav Kumar Mishra Neeraj Kumar Zsolt Tóth Yousef A. Bin Jardan Shopnil Akash John J. Georrge Unveiling the molecular activity of HIV towards the CD4: A study based on subtype C via docking and dynamics approach Journal of Genetic Engineering and Biotechnology HIV subtype C CD4 receptor Docking PCA Molecular dynamics simulation |
| title | Unveiling the molecular activity of HIV towards the CD4: A study based on subtype C via docking and dynamics approach |
| title_full | Unveiling the molecular activity of HIV towards the CD4: A study based on subtype C via docking and dynamics approach |
| title_fullStr | Unveiling the molecular activity of HIV towards the CD4: A study based on subtype C via docking and dynamics approach |
| title_full_unstemmed | Unveiling the molecular activity of HIV towards the CD4: A study based on subtype C via docking and dynamics approach |
| title_short | Unveiling the molecular activity of HIV towards the CD4: A study based on subtype C via docking and dynamics approach |
| title_sort | unveiling the molecular activity of hiv towards the cd4 a study based on subtype c via docking and dynamics approach |
| topic | HIV subtype C CD4 receptor Docking PCA Molecular dynamics simulation |
| url | http://www.sciencedirect.com/science/article/pii/S1687157X25000010 |
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