RESUMEN
We review the development and application of the Simplex approach for the solution of various QSAR/QSPR problems. The general concept of the simplex method and its varieties are described. The advantages of utilizing this methodology, especially for the interpretation of QSAR/QSPR models, are presented in comparison to other fragmentary methods of molecular structure representation. The utility of SiRMS is demonstrated not only in the standard QSAR/QSPR applications, but also for mixtures, polymers, materials, and other complex systems. In addition to many different types of biological activity (antiviral, antimicrobial, antitumor, psychotropic, analgesic, etc.), toxicity and bioavailability, the review examines the simulation of important properties, such as water solubility, lipophilicity, as well as luminescence, and thermodynamic properties (melting and boiling temperatures, critical parameters, etc.). This review focuses on the stereochemical description of molecules within the simplex approach and details the possibilities of universal molecular stereo-analysis and stereochemical configuration description, along with stereo-isomerization mechanism and molecular fragment "topography" identification.
RESUMEN
This paper describes the Structural and Physico-Chemical Interpretation (SPCI) approach, which is an extension of a recently reported method for interpretation of quantitative structure-activity relationship (QSAR) models. This approach can efficiently be used to reveal structural motifs and the major physicochemical factors affecting the investigated properties. Its efficacy was demonstrated both on the classical Free-Wilson data set and on several data sets with different end points (permeability of the blood-brain barrier, fibrinogen receptor antagonists, acute oral toxicity). Structure-activity patterns extracted from QSAR models with SPCI were in good correspondence with experimentally observed relationships and molecular docking, regardless of the machine learning method used. Comparison of SPCI with the matched molecular pair (MMP) method clearly shows an advantage of our approach over MMP, especially for small or structurally diverse data sets. The developed approach has been implemented in the SPCI software tool with a graphical user interface, which is publicly available at http://qsar4u.com/pages/sirms_qsar.php .