The non-structural dengue virus (DNV) protein, DNV-2 NS2B/NS3 protease is a combination of two proteins as 2B and 3 and these two proteins in complex replicate faster during dengue fever. The objective of the present study was to detect hot spots and design of smart libraries for engineering protein stability, substrate specificity, tunnels and cavities as well as suitable mutability position of studied protein by using an online tool, HotSpot Wizard (version 3.0). The prediction results were obtained in output interface for functional hot spots, stability hot spots (structural flexibility), correlated hot spots and stability hot spots (sequence consensus) from the sequence string. It is concluded that the prediction of pocket and mutability of this protein can easily be identified the structural alternation especially in disease diagnosis and space for ligand binding site in pocket for the potential of new drug design. Moreover, this computational prediction is suggested to compare with experimental hotspots for studied protein in relation to therapeutic efficacies, which are lacking to prevent viral infection.
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