Iterative Screening Methods for Identification of Chemical Compounds with Specific Values of Various Properties

Identification of chemical compounds having desirable properties is a central goal of screening campaigns. Iterative screening is a means of surveying a set of compounds, during which their property values are determined and used as feedback for regression models. Quantitative models that assess the relationships between chemical structures and property/activity are repeatedly updated through this type of cycle, and the efficient sampling of compounds for the subsequent test is a key factor in the early identification of target compounds. Nevertheless, methodological approaches to comparisons and to establishing the degree of extrapolation of sampled compounds, including the effects of applicability domains, are still required. In the present study, we conducted a series of virtual experiments to assess the characteristics of different iterative screening methods. Genetic algorithm-based partial least-squares regression, support vector regression, Bayesian optimization with Gaussian Process (GP), and batch-based Bayesian optimization with GP (GP_batch) were all compared, based on the analysis of one million compounds extracted from the ZINC database. Our results show that, irrespective of the diversity of the initial set of compounds, it was possible to identify a compound having the desired property value using the appropriate screening method. However, overall, the GP_batch method was found to be preferable when evaluating properties either which are difficult to predict or for which a key factor is present in the set of molecular descriptors.