Practical recommendations – virtual screening hit selection and optimisation based on a literature analysis


Virtual screening is a part of modern drug discovery and has received much attention in the literature. The publications to date however largely focus on case studies or descriptions of methodologies and there are no reported views or guidelines on hit selection or optimisation critieria which exist for conventional screening. A recent publication (Zhu et al – Hit Identification and Optimization in Virtual Screening: Practical Recommendations Based on a Critical Literature Analysis ) highlights this issue and seeks to address the gap based upon a thorough review of the literature from 2007 to 2011.

The groups finding are interesting and their conclusions valuable to the practising medicinal chemist.

They found that whilst potency criteria varied the majority of groups employed potency cut offs in the low to mid micromolar range(1-100uM) similar to groups engaged in hit identification via conventional HTS.Another perhaps more disturbing trend observed was that groups were not using physicochemical filters or structural alerts as widely as might expected And they recommend the inclusion of ligand efficiency criteria and application of a structural alert filter.This observation is perhaps some what surprising given the number of recent publications highlighting the dangers of high lipophilicity etc and it would seem that too many chemists are still being seduced by potency and ignoring other important considerations. Another interesting observation is that typical hit rates for virtual screens are highly than those for high throughput screens.

The authors conclude by making some simple and logical recommendations for workers to use in association with future virtual screening campaigns amongst them they emphasise the need to include physico – chemical property filters and further qualify this by pointing out that certain newer target classes may require higher molecular weight ligands

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