Modeling Choices for Virtual Screening Hit Identification

Making suitable modeling choices is crucial for successful in silico drug design, and one of the most important of these is the proper extraction and curation of data from qHTS screens, and the use of optimized statistical learning methods to obtain valid models. More specifically, we aim to learn the top‐1 % most potent compounds against a variety of targets in a procedure we call virtual screening hit identification (VISHID). To do so, we exploit quantitative high‐throughput screens (qHTS) obtained from PubChem, descriptors derived from molecular structures, and support vector machines (SVM) for model generation. Our results illustrate how an appreciation of subtle issues underlying qHTS data extraction and the resulting SVM models created using these data can enhance the effectiveness of solutions and, in doing so, accelerate drug discovery.