Predicting Drug Targets from Hypothetical Proteins of Pseudomonas Sp. Released from Permafrost Thawing under Impact of Climate Change

One of the major consequences of the increase in global temperature is the thawing of permafrost, which is predicted to cause huge imbalances in natural ecosystems. The results of permafrost thawing is the resurface of quiescent psychrotolerant microbes which have been shown to be storehouses of antibiotic resistance genes (ARGs). Such superbugs, even if non-pathogenic, can transfer the ARGs to active pathogens, aggravating the existing public health crisis of antibiotic resistance. It is thus imperative to explore novel drug targets. Like most other organisms, bacteria possess coding sequences in the genome whose cellular and biochemical functions remain to be predicted. Functional annotation of such hypothetical proteins and their subsequent exploration as drug targets can thus be attempted as a novel computer-aided drug discovery approach. In this paper, we propose an in-silico pipeline for characterisation and functional annotation of hypothetical proteins using Pseudomonas aeruginosa, a multidrug-resistant WHO-listed critical priority pathogen. We then explore their potential as drug targets with small molecules of plant origin. Our results show considerable interactions between the proteins and the small molecules, including successful molecular docking, establishing a successful pipeline which may be useful in small molecule-based drug discovery in the near future.