Computer-aided prediction of biological activity spectra for organic compounds: the possibilities and limitations

Abstract

We describe the current version of the PASS program for prediction of biological activity spectra of organic compounds based on analysis of structure—activity relationships (SAR) for a training set containing information on more than 1000 000 biologically active organic compounds. The average accuracy of prediction for more than 5 000 types of biological activity exceeds a value of 0.96. To analyze quantitative SAR, the GUSAR program was developed. The advantages of GUSAR were demonstrated in a number of computational experiments. The local versions of the PASS and GUSAR programs, as well as 19 freely available web services were developed. The latter are freely accessible via the Internet at http://way2drug.com/dr. The web services at the Way2Drug portal are used by more than 24 000 researchers working in about 100 countries. Currently, more than 830 000 predictions were made, the most promising compounds were selected for chemical synthesis, and priorities for testing their biological activity were established. The PharmaExpert software was developed to analyze the results of the PASS- and GUSAR-based predictions and to search for chemical compounds with necessary biological activity spectra. Combined use of the PASS, GUSAR, and PharmaExpert programs enables an assessment of the pharmacotherapeutic, adverse, and toxic effects of new compounds based on the systems pharmacology.