Department of Physics, Bharathiar University, Coimbatore, India.
Department of Medical Physics, Bharathiar University, Coimbatore, India.
J Biomol Struct Dyn. 2021 Apr;39(6):1912-1927. doi: 10.1080/07391102.2020.1742205. Epub 2020 Apr 6.
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.
登革热病毒正在成为一种主要的全球疾病；包膜蛋白是针对登革热开发疫苗的主要目标。如今，人们的注意力集中在开发基于木瓜蛋白酶的抑制剂上，木瓜蛋白酶是治疗登革热的一个有前途的靶点。在目前的工作中，通过密度泛函理论（M06-2X/cc-pVDZ）方法分析了 E 蛋白（Cys74-Glu79；Lys110）…木瓜蛋白酶（Cys25、Asn175 和 His159）复合物的理论研究。在 E 蛋白（Cys74-Glu79；Lys110）…木瓜蛋白酶（Cys25、Asn175 和 His159）复合物中，E 蛋白（Glu76）…木瓜蛋白酶（Cys25）复合物的相互作用值最高，为-352.22 kcal/mol。此外，自然键轨道分析也支持上述结果。100 ns 分子动力学模拟表明，与 E 蛋白（Ala54-Ile129）…木瓜蛋白酶（Asn175 & His159）复合物相比，E 蛋白（Ala54-Ile129）…木瓜蛋白酶（Cys25）复合物的均方根偏差值最低，为 1 Å。Asp103 和 Lys110 残基之间形成的盐桥是 E 蛋白（Ala54-Ile129）…木瓜蛋白酶（Cys25）复合物的重要稳定因素。这一结果可以扩展我们对木瓜蛋白酶功能行为的认识，并为以包膜蛋白为靶点的未来药物提供结构见解。
