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 for therapeutic usage. In the present
work, we address this question by analyzing the functional groups
of these molecules and the interactions they display in a set of more
than 71K protein–metabolite interactions from the PDB. Significant
differences in the functional group distributions, their chemical
features, and their co-occurrences are observed for distinct subsets
of these molecules. The same is true for the distributions of interaction
types. By correlating both data sets, we are able to explain the observed
interaction patterns in terms of observed functional group patterns.
These results will shed light on the rational design of novel metabolite
mimetic molecules for therapeutic purposes.