Application of the Weighted Power-Weakness Ratio (wPWR) as a Fusion Rule in Ligand–Based Virtual Screening
Matteo Cassotti, Francesca Grisoni, Serena Nembri, Roberto Todeschini · BOA (University of Milano-Bicocca) · 2016
Similarity searching, a technique used for ligand-based virtual screening in drug discovery, exploits the structural information of known active compounds to find new ones with the desired biological activity. The effectiveness of similarity searching can be enhanced by combining independent searches, executed with different reference structures, through the socalled fusion rules. In this pilot study, we applied for the first time the weighted Power- Weakness Ratio (wPWR) as a fusion rule. wPWR was recently proposed as a multi-criteria decision-making and ranking comparison technique that, unlike existing parameter-free fusion rules, (1) is based on pairwise comparisons between compounds, and (2) can use weighting schemes. We compared wPWR with six fusion rules on four datasets using six evaluation metrics. The results indicated that wPWR has a mediocre performance but also the most robust behavior. Moreover, in one case, wPWR had the best accumulation curve on the top 25 compounds. These aspects are important for prospective applications. Weighting the reference structures according to their activity did not show a net beneficial effect on one analyzed dataset and, thus, further investigations are needed.