Use of Computational Models to Investigate Human Targets of Small Ubiquitous Molecules

利用计算模型研究小分子普遍存在的人体靶点

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Abstract

The effects on human health of chemical compounds, which might be present in the environment due to natural or anthropogenic causes, are a fundamental aspect to be considered for the protection of public health and workers' health and in the evaluation of industrial processes in terms of health protection and sustainability. Investigations focused on lesser known effects that have recently drawn more attention on potential human target proteins. Due to the complexity of biochemical interactions, it is not straightforward to determine the biological response resulting from exposure to a specific chemical. In this article, we tackle this issue by combining chemoinformatics tools and atomistic modeling to perform target identification for several compounds. The study was carried out using a publicly available database that collects relationships between chemicals, genes, and phenotypes and resulting diseases to validate the results of the target identification pipeline. Small molecules that may occur in occupational and nonoccupational settings were investigated. Finally, we discuss the potentialities and limitations of using these fast, computationally inexpensive methods in early-stage target identification, both with and without performing a literature search for experimental data.

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