The in chemico-in silico interface: Challenges for integrating experimental and computational chemistry to identify toxicity

Abstract

A number of toxic effects are brought about by the covalent interaction between the toxicant and biological macromolecules. In chemico assays are available that attempt to identify reactive compounds. These approaches have been developed independently for pharmaceuticals and for other non-pharmaceutical compounds. The assays vary widely in terms of the macromolecule (typically a peptide) and the analytical technique utilised. For both sets of methods, there are great opportunities to capture in chemico information by using in silico methods to provide computational tools for screening purposes. In order to use these in chemico and in silico methods, integrated testing strategies are required for individual toxicity endpoints. The potential for the use of these approaches is described, and a number of recommendations to improve this extremely useful technique, in terms of implementing the Three Rs in toxicity testing, are presented.