Philippine E-Journals

Model Prediction and Molecular Docking Simulations of a Novel Cone Snail Toxin, tcon-1

A. P. Limpot | N.a. D. Bascos | C.P Saloma

 

Abstract:

Venom from terrestrial and aquatic animals has always been a source of fear for mankind, but studies have shown that this cocktail of toxins is a rich source of potential pharmacological molecules. Predatory marine snails are known to harbor potent toxins in their venom that elicit an array of physiological phenomena, one of which has already been developed into a commercial analgesic. A novel cone snail toxin, tcon-1, was discovered through the transcriptomic analysis of three marine snails (C. cerithina, U. bisaya, and G. speciosa) and was subsequently characterized in silico and expressed in vitro. The initial in silico analysis revealed that tcon-1 is a structural analog of a previously described Conus striatus toxin called con-ikot-ikot. In this study, a protein model of tcon-1 was predicted by I-TASSER and subsequently docked unto the con-ikot-ikot target receptor. A dimerized model of tcon-1 was utilized in the molecular docking simulations against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) using ClusPro. The docking results show that tcon-1 binds to similar regions as con-ikot-ikot in its putative target receptor, the AMPAR. Succeeding in vitro experiments relating to these observed similarities will shed light on the validity of the predicted functional mechanism of tcon-1 action.