Mael Briand

We investigate the representation of atomic molecular environments as a list of the atoms neighboring an origin ranked by distance. We show that contact densities collected for origin-neighbor pairs of set types have regular and specific distributions when stratified by ranks. This is used to build a scoring function assessing the fitness of individual atoms with respect to their environment (FS, fitness score), as well as to characterize the contact preferences (CP) for pairs of atoms. Tested against the 3DRobot data set, the FS score was found to be highly discriminative of decoys vs native X-ray. The code is freely available on GitHub (https://github.com/DreanoLoic/Fitness_score.git).

EcoDrug PLUS (EcoDrug+; https://ecodrugplus.helsinki.fi/) is a freely available and publicly accessible database, established to facilitate environmental risk assessment of pharmaceuticals and other bioactive substances, including veterinary medicines and pesticides. EcoDrug+ advancements on the original ECODrug database include a more extensive and intuitive graphical user interface for investigating the potential for chemicals to interact with protein targets based on their conservation with human drug, veterinary, and pesticide targets across 180 phylogenetically diverse wildlife taxa. EcoDrug+ integrates genomic and chemoinformatic data from open-access sources for ~7200 pharmaceuticals, 34 000 agrochemicals, 61 000 human metabolites, and 5800 other bioactive chemicals. Advanced search capabilities of EcoDrug+ include the ability to interrogate the database via text queries, chemical structure drawings, target protein sequence BLAST, and/or specified mechanisms of action. Chemical compound data are organized into clusters to facilitate the exploration of similar groups using interactive knowledge graphs. The integration of effects-based knowledge informs on appropriate endpoints and susceptible species for the testing of drugs (and other bioactive chemicals). Georeferenced measured environmental concentrations (for n = 266 chemicals) furthermore provide relevant exposure data for testing and environmental risk analysis.

Cooperative molecular contacts play an important role in protein structure and ligand binding. Here, we constructed a PostgreSQL database that stores structural information in the form of atomic environments and allows flexible mining of molecular contacts. Taking the Ser‐His‐Asp/Glu catalytic triad as a first test case, we demonstrate that the presence of a carboxylate oxygen atom in the vicinity of a His is associated with shorter Ser‐OH..N‐His bond in the PDB30 subset. We prospectively mine catalytic triads in unannotated proteins, suggesting catalytic functions for unannotated proteins. As a second test case, we demonstrate that this database system can include ligand atoms, represented by Sybyl atom types, by evaluating the proportion of counter‐ions for ligand carboxylate oxygens.