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Abstract
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 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 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 datasets, 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.
Supplementary materials
Title
Supporting Information (Table S1)
Description
Table S1: Matching of FGs with BINANA 2 interactions. For each PDB entry id, ligand instance, and FG instance, the presence or absence of interactions for the eight interaction types is denoted by 1 or 0, respectively. Column description: “entry_id”: Entry ID of the PDB structure; “lig_id: ligand ID of the ligand in the PDB entry; “comp_set”: compound set of the ligand; “fgs”: list of atom indexes comprising the FG; “psmis”: pseudo-SMILES code of the FG; “closest”: presence / absence of closest interaction; “hydrophobics”: presence / absence of hydrophobics interaction, “hydrogen_bonds”: presence / absence of hydrogen bonds interaction; “halogen_bonds”: presence / absence of halogen bonds interaction; “pi_pi”: presence / absence of pi-pi interaction; “cat_pi”: presence / absence of cation-pi interaction; “salt_bridges”: presence / absence of salt bridges interaction; “metal_coordinations”: presence / absence of metal coordinations interaction.
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