Abstract Background Traditional quantitative structure-activity relationship models usually neglect the molecular alterations happening in the exposed systems (the mechanism of action, MOA), that mediate between structural properties of compounds and phenotypic effects of an exposure. Results Here, we propose a computational strategy that integrates molecular descriptors and MOA information to better explain the mechanisms underlying biological endpoints of interest. By applying our methodology, we obtained a statistically robust and validated model to predict the binding affinity to human serum albumin. Our model is also able to provide new venues for the interpretation of the chemical-biological interactions. Conclusion Our observations suggest that integrated quantitative models of structural and MOA-activity relationships are promising complementary tools in the arsenal of strategies aiming at developing new safe- and useful-by-design compounds.

2019