Classification of Staphylococcus Aureus FabI Inhibitors by Machine Learning Techniques

Abstract

Enoyl-acyl carrier protein reductase (FabI) is a key enzyme in the fatty acid metabolism of gram-positive bacteria and is considered a potential target for new antibacterial drugs development. Indeed, triclosan is a widely employed antibacterial and AFN-1252 is currently under phase-II clinical trials, both are known as FabI inhibitors. Nowadays, there is an urgent need for new drug discovery due to increasing antibacterial resistance. In the present study, classification models using machine learning techniques were generated to distinguish SaFabI inhibitors from non-inhibitors successfully (e.g., Mathews correlation coefficient values equal to 0.837 and 0.789 calculated with internal and external validations). The interpretation of a selected model indicates that larger compounds, number of N atoms and the distance between central amide and naphthyridinone ring are important to biological activity, corroborating previous studies. Therefore, these obtained information and generated models can be useful for design/discovery of novel bioactive ligands as potential antibacterial agents.