Toward a Computational Ecotoxicity Assay

doi:10.1021/acs.jcim.0c00574

2020-07-10

Natasha Kamerlin

Mickaël G. Delcey

Sergio Manzetti

David van der Spoel *

DOI：10.1021/acs.jcim.0c00574

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摘要

En 中文

Thousands of anthropogenic chemicals are released into the environment each year, posing potential hazards to human and environmental health. Toxic chemicals may cause a variety of adverse health effects, triggering immediate symptoms or delayed effects over longer periods of time. It is thus crucial to develop methods that can rapidly screen and predict the toxicity of chemicals to limit the potential harmful impacts of chemical pollutants. Computational methods are being increasingly used in toxicity predictions. Here, the method of molecular docking is assessed for screening potential toxicity of a variety of xenobiotic compounds, including pesticides, pharmaceuticals, pollutants, and toxins derived from the chemical industry. The method predicts the binding energy of pollutants to a set of carefully selected receptors under the assumption that toxicity in many cases is related to interference with biochemical pathways. The strength of the applied method lies in its rapid generation of interaction maps between potential toxins and the targeted enzymes, which could quickly yield molecular-level information and insight into potential perturbation pathways, aiding in the prioritization of chemicals for further tests. Two scoring functions are compared: Autodock Vina and the machine-learning scoring function RF-Score-VS. The results are promising, although hampered by the accuracy of the scoring functions. The strengths and weaknesses of the docking protocol are discussed, as well as future directions for improving the accuracy for the purpose of toxicity predictions.

Keyword:

FREE-ENERGY CALCULATIONS

EXPLICIT SOLVENT MODELS

IN-SILICO PREDICTION

MOLECULAR DOCKING

PERFLUOROOCTANOIC ACID

SCORING FUNCTIONS

BINDING-AFFINITY

RECEPTORS ALPHA

BLIND DOCKING

TOXICITY