How Do Microbial Metabolites Interact with Their Protein Targets?

The design of drugs and nutraceutics that mimic microbial metabolites is an emerging drug modality in medicinal chemistry that attempts to modulate the myriad of interactions that these molecules establish with host and microbial proteins. Understanding how microbial metabolites interact with their target proteins is key to perform a rational design of metabolite mimetic molecules with therapeutic usage. In the present work we answer that question by analyzing the functional groups of these molecules, and the interactions they display in a set of more than 71 K protein-metabolite interactions from the PDB. Significant differences in the functional groups distributions, their chemical features, and their co-ocurrences, are observed for distinct subsets of these molecules. The same is true for the distributions of interaction types. By correlating both datasets, we are able to explain the observed interaction patterns in terms of observed functional group patters. These results will shed light on the rational design of novel metabolite mimetic molecules for therapeutic purposes.

Here, we provide the 71K prepared .pdbqt files of proteins and ligands used to analyze the interactions between them.