In silico prospection of receptors associated with the biological activity of U1-SCTRX-lg1a: an antimicrobial peptide isolated from the venom of Loxosceles gaucho

Abstract

Background: The emergence of antibiotic-resistant pathogens generates impairment to human health. U1-SCTRX-lg1a is a peptide isolated from a phospholipase D extracted from the spider venom of Loxosceles gaucho with antimicrobial activity against Gram-negative bacteria (between 1.15 μM to 4.6 μM). The aim of this study was to suggest potential receptors associated with the antimicrobial activity of U1-SCTRX-lg1a using in silico bioinformatics tools. Methods: The search for potential targets of U1-SCRTX-lg1a was performed using the PharmMapper server. Molecular docking between U1-SCRTX-lg1a and the receptor was performed using PatchDock software. The prediction of ligand sites for each receptor was conducted using the PDBSum server. Chimera 1.6 software was used to perform molecular dynamics simulations only for the best dock score receptor. In addition, U1-SCRTX-lg1a and native ligand interactions were compared using AutoDock Vina software. Finally, predicted interactions were compared with the ligand site previously described in the literature. Results and discussion: The bioprospecting of U1-SCRTX-lg1a resulted in the identification of forty-nine intracellular proteins originating from Gram-negative microorganisms. Among these, NH3-dependent NAD+ synthetase showed the highest dock score. This result suggests that the peptide derived from brown spider venom may interact with residues SER48 and THR160. In addition, the C-terminus has greater affinity for the receptor than the N-terminus. Conclusion: The in silico bioprospecting of receptors suggests that U1-SCRTX-lg1a may interfere with NAD+ production in Escherichia coli, a Gram-negative bacterium, altering the homeostasis of the microorganism and impairing growth.

In silico bioprospecting of receptors for Oligoventin: an antimicrobial peptide isolated from spider eggs of Phoneutria nigriventer

“…These tools are commonly used in protein chemistry, enabling the evaluation of molecular threedimensional structure, folding, interactions, docking, and dynamics (14)(15)(16)(17). In silico methods offer the principal advantage of reducing the time and cost associated with screening assays.…”