Predicting undesirable drug interactions with promiscuous proteins in silico

Although computational tools have been used to predict toxic responses resulting from molecules binding either as substrates or inhibitors to proteins, there are complications to be resolved. Some proteins appear promiscuous in their ability to bind a diverse array of hydrophobic molecules. This promiscuity arises from the binding site simultaneously accommodating more than one molecule, multiple separate binding sites, protein flexibility, or a combination of all these properties. With the availability of more crystal structures for these non-target proteins, we should be able to predict binding in silico with a greater accuracy, thus avoiding or managing toxic side effects, therefore ultimately improving the success of drug discovery. In silico approaches for predicting drug interactions with promiscuous proteins have been developed and these represent a first step to screening molecules before synthesis.