Targeting the Bap1 protein of Vibrio cholerae for screening potent inhibitors and predicting the mutant protein stability: in silico analyses

Abstract

Background: Bap1 is reported to be a major protein in Vibrio cholerae which aids in biofilm formation. Hence, inhibition of the protein molecule can no longer support the colonization of bacteria and induction of point mutations at specific amino acid residues tend to reduce the protein stabilization. The aim of the study: To target this Bap1 structural protein for screening potent inhibitors of ligands by means of in silico analyses. Materials and methods: A total of 30 compounds divided into three groups such as synthetic antimicrobial drugs, phytochemicals and marine compounds comprising of ten ligands in each group were tested against Bap1. In addition to this, mutations were induced at GLN: 518, HIS: 520 and ASN: 679 positions to determine the stability of the mutant Bap1 protein using bioinformatic tools. Results: Of the 30 docked compounds, doxycycline, ichangin and Ageloxime D exhibited the highest binding affinities of -8.5 kcal/mol, -9.3 kcal/mol and -8.8 kcal/mol respectively from the three groups. The ADME properties show the druglikeness of the test compounds to be used for treatment procedures. Protein-ligand interactions were visualized which infer that both doxycycline and ichangin form five conventional hydrogen bonds while Ageloxime D could form three hydrogen bonds with different amino acid residues of the protein. Further, the van der Waals’ interactions are also found to be similar in number among doxycycline and ichangin whereas, it is less in case of Ageloxime D but, the π- interactions are high in this compound comparatively. The carbon-hydrogen bonding for these three compounds with the amino acid residues of the Bap1 protein have also been discussed. Conclusion: Thus, natural compounds can eventually replace the over use of synthetic drugs as antibiofilm agents. Also, inducing point mutations to this protein can potentially destabilize its structure.