Multivariate analysis in the identification of biological targets for designed molecular structures: The BIOTA protocol

Abstract

In this work the new protocol BIOlogical Target Assignation (BIOTA) for the prediction of the biological target from molecular structures is proposed. BIOTA is based on the Principal Components Analysis (PCA) application on a matrix of ligands versus molecular descriptors. The application of BIOTA could allow to hypothesize the mechanism of action of a candidate drug prior to its biological evaluation or to repurpose old drugs. The protocol can be fine-tuned by choosing opportune targets (biological or not) and molecular descriptors, and it can be useful in every fields in with it is possible to collect set of compounds with known properties. The robustness of the protocol depends from different factors: the correctness of biological data, the optimization of the molecular structures and their molecular descriptors calculation, the selection of the biological targets. The application of BIOTA to a new class of Hsp90 inhibitors was able to predict quite correctly their affinity for Hsp90