In-silico Drug Design and in-silico screening  (Track)

DEVELOPMENT OF CUSTOMIZED COMPOUND DIVERSITY SETS AND IDENTIFICATION OF FREQUENT HITTERS IN MOLECULAR AND VIRTUAL SCREENING

Iryna O. Lebedyevaand Thomas Albers

Augusta University, 1120 15th Street, Augusta GA 30912, USA

Abstract

The “screen less, get more hits of better quality” paradigm has been employed to: i) eliminate compounds with reactive, UGLY and undesirable functional groups; ii) eliminate potentially unstable at acidic condition compounds, some imines, pyrimidine-triones; iii) enrich the set with non-amide and non-urea containing compounds (50:50 ratio), and iv) create a smaller and convenient for use compound set for high quality hit identification.

In order to identify frequent compound hitters, virtual screening has been done employing the NCI Diversity Set V against 11 structurally and functionally diverse protein target binding sites. A method to detect frequent hitters by scoring the presence or absence of features in Daylight-like fingerprints in selective versus unselective hits was developed. This approach can be used in the design of chemical libraries for virtual screening.

The developed approaches allow for identification and elimination of promiscuous and false positive compounds in virtual screening. These methods also increase the quality of customized compound libraries and diversify the chemical space for the novel inhibitors. This approach can be used in the design of chemical libraries for virtual screening.