Comprehending the outer membrane protein modelling of pathogenic Gram-negative bacteria for <i>in silico</i> antibiotics screening

Pathogenic Gram-negative Bacteria (GNB) continue to become a major challenge in the modern public health, as the development of new antibacterials against pathogenic GNB is hindered by the emergence of multidrug-resistant (MDR) strains. Thus, the discovery of new antibacterial drugs to overcome the MDR bacteria must remain an ongoing effort. One of the promising strategies is to utilize computational molecular simulations to understand interactions between the target protein and various drug candidates. β-barrel assembly machinery subunit A (BamA) has recently gained attention as a potential target protein. Yet, the availability of the 3D structure of the protein from various species of GNB is still limited and hinders the drug discovery studies. In this study, a pipeline to construct BamA protein model from pathogenic MDR strains of Klebsiella pneumoniae HS11286 and Shigella flexneri A was established using Modeller 10.5, followed by refinement and models evaluations. The BamA sequences from K. pneumoniae and S. flexneri used in this pipeline shared about 91.01% and 99.75% identity, subsequently, with BamA from Escherichia coli K12. The final refined models of BamA proteins from both bacteria showed optimal structural characteristics, as reflected in all assessment parameters. Thus, the modelling pipeline performed in this preliminary study is promising to facilitate the in-silico screening study in searching for new antibiotics for combating Gram-negative pathogens.