Internet laboratory for predicting harmful effects triggered by drugs and chemicals. Concept and call for co-operation

Abstract

It is our objective to establish a virtual laboratory on the Internet to allow for an in silico estimation of harmful effects triggered by drugs, chemicals and their metabolites. Presently, our database includes validated models for five biological targets - the Aryl hydrocarbon, serotonin 5HT-2A, cannabinoid, GABA (gamma-amino butter acid), and steroid receptors. It shall be continuously extended to include surrogates for any bioregulator known or presumed to mediate harmful effects. Free access to this virtual laboratory shall allow any interested party to estimate the harmful potential of a given substance prior to its synthesis. This is achieved by generating the three-dimensional structure of the compound and its possible metabolites in the computer, followed by calculating their binding affinity towards each receptor surrogate in the database. Only compounds/metabolites passing through this surrogate battery without displaying a significant affinity towards any member may be cleared for synthesis and preclinical studies. This way, potentially harmful compounds can be withdrawn from the evaluation pipeline before in vivo test are conducted, hence contributing to the reduction of animal testing in chemical and pharmaceutical research and development.