Bridging Chemical and Biological Space: QSAR Probing Using 3D Molecular Descriptors

Quantitative Structure-Activity Relationships (QSAR) modeling tools play a critical role today in both drug design and environmental sciences. QSAR modeling seeks to discover and use mathematical relationships between molecular properties of the compounds (descriptors) and the often complex activity of interest. An extensive number of molecular descriptors exist which can and have been used to model a wide range of target activities. This complicates the task of selecting those that will be more suitable, especially when one tries to define an accurate, robust, predictive and (most importantly) interpretable model. Lately, recognition of the importance of the three-dimensionally (3D) structure and stereochemistry of molecules to their biological activity, and awareness of the limitations of classical approaches, led to many attempts to generate 3D descriptors either as a complement for 2D-QSAR models or for standalone 3D-QSAR models. This review describes the 3D descriptors available in the DRAGON software along with their successful applications primarily in Medicinal Chemistry, updating a previously published paper in Current Topics in Medicinal Chemistry (Helguera, A.M.; Combes, R.D.; González, M.P.; Cordeiro, M.N.D.S., 2008, 8, 1628-1655).

Keywords: DRAGON software, 3D-descriptors, enzymatic inhibition, receptors affinity and selectivity, anticancer, anti-microbial, ADME/Tox.