| Popis: |
Three-finger toxin (short and long neurotoxins) belongs to a super-family of non-enzymatic proteins found in all families of snakes. They have common three-dimensional structures of three beta-stranded loops extending from a central core containing all four conserved disulphide bonds. Despite the common scaffold, they bind to neuronal and muscle receptors with varying binding affinities and exhibit a wide variety of biological activities. In the present studies, we have mapped the binding site residues on short and long neurotoxins by analyzing the docking models of the proteins with nicotinic acetylcholine receptors (nAChRs). Moreover, binding modes for tens of small molecules have been studied on both types of neurotoxins and could be classified as either competitive or allosteric antagonists. Two top-ranked lead compounds that may act as competitive antagonists to the neurotoxins were chosen and used to construct a combinatorial library containing 600 small molecules by using LigBuilder. In order to identify high-efficient de novo lead compounds from the combinatorial library, the compounds were subjected to high throughput virtual screening by using PyRx and Glide-HTVS docking tools. The top ten de novo lead compounds that may be developed as high-efficient anti-venom compounds to neurotoxins from elapidae family have been brought into fore and their structural features are also discussed in detail |
