Bioinformatics Approach on Hypothetical Protein from Clostridioides difficile: Structural, Functional and Molecular Docking Analysis

Abstract

Clostridioides difficile (C. difficile) has become a globally important pathogen as epidemic strains spread through hospitals in many countries. Despite the advancements in infection therapy, there is a need for more efficacious medicines against C. difficile that simultaneously minimize injury to the resident gut microbiota. The study aims to investigate various aspects of the protein, including its physicochemical properties, subcellular location, functional elucidation, protein-protein interactions, structure prediction, validation, determination of active sites for potential ligands, and MD study. The protein is partially basic and hydrophobic, according to the physicochemical properties analysis. The protein has activities in the inner membrane and the cytoplasm with two transmembrane helices. Furthermore, the protein is involved in secondary transporters in the MFS system, resulting in the movement of various substances through cytoplasmic or internal membranes. We targeted the active sites of the protein as potential binding sites for ligand molecules to discover novel therapeutic agents. The MD study documented the interaction of the selected ligands (PA{beta}N and CCCP) with the protein. PA{beta}N demonstrated the most suitable ligand compared to CCCP, as it required the lowest energy (- 6.7 kcal/mol) to interact with the protein. This functional protein can be targeted for further study on potential therapeutic candidates against the protein of C. difficile.