Multiple Linear Regression Model of Thermolysin Inhibitors
2 Bioinformatic Research in Systems & Computer Engineering, Carleton University, Ottawa, Canada
3 Centro Interdisciplinario de Neurociencia de Valparaiso, Facultad de Ciencias, Universidad de Valparaiso, Valparaiso, Chile
4 Doctorado en Fisicoquimica Molecular, Center of Applied Nanosciences (CENAP), Universidad Andres Bello, Ave. Republica 275, Santiago, Chile
5 Institut Universitari de Ciència Molecular, Universitat de València, Edifici d'Instituts de Paterna, P. O. Box 22085, 46071 Valencia, Spain
* Author to whom correspondence should be addressed.
Thermolysin is a bacterial proteolytic enzyme, considered by many authors as a pharmacological and biological model of other mammalian enzymes, with similar structural characteristics, such as Angiotensin Converting Enzyme and Neutral Endopeptidase. Inhibitors of these enzymes are considered therapeutic targets for common diseases, such as hypertension and heart failure. In this report, a mathematical model of Multiple Linear Regression, for ordinary least squares, and genetic algorithm, for selection of variables, are developed and implemented in QSARINS software, with appropriate parameters for its fitting. The model is extensively validated according to OECD standards, so that its robustness, stability, low correlation of descriptors and good predictive power are proven. In addition, it is found that the model fit is not the product of a random correlation. Two possible outliers are identified in the model application domain but, in a molecular docking study, they show good activity, so we decide to keep both in our database. The obtained model can be used for the virtual screening of compounds, in order to identify new active molecules.