In silico studies of the inhibition mechanism of dengue with papain. Issue 6 (31st March 2021)

• Record Type: Journal Article
• Authors: Saranya, Vasudevan; Radhika, Ramachandran; Shankar, Ramasamy; Vijayakumar, Subramaniam
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 39:Issue 6(2021)
• Page Start: 1912
• Page End: 1927
• Publication Date: 2021-03-31
• Subjects: Dengue -- molecular dynamics -- papain -- inhibitor -- envelope protein -- salt bridge -- anti-dengue activity; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2020.1742205
• Languages: English
• ISSNs: 0739-1102

Abstract

Abstract: Dengue virus is becoming a major global disease; the envelope protein is the major target for vaccine development against Dengue. Nowadays, the attention has focused on developing inhibitors based on Papain is a promising target for treating Dengue. In the present work, the theoretical studies of E-protein(Cys74-Glu79;Lys110)…Papain(Cys25, Asn175 and His159) complexes are analysed by Density Functional Theory (M06-2X/cc-pVDZ) method. Among the E-protein(Cys74-Glu79;Lys110)…Papain(Cys25, Asn175 and Hys159) complexes, E-protein(Glu76)…Papain(Cys25) complex has the highest interaction value of −352.22 kcal/mol. Moreover, the natural bond orbital analysis also supports the above results. The 100 ns Molecular Dynamics simulation reveals that, E-protein(Ala54-Ile129)…Papain(Cys25) complex had the lowest root mean square deviation value of 1 Å compared to the E-protein(Ala54-Ile129)… Papain(Asn175 & His159) complexes. The salt bridge formation between the Asp103 and Lys110 residues are the important stabilizing factor in E-protein(Ala54-Ile129)…Papain(Cys25) complex. This result can extend our knowledge of the functional behaviour of Papain and provides structural insight to target Envelope protein as forthcoming drug targets in Dengue. Graphical Abstract: Communicated by Ramaswamy H. Sarma