Effectiveness of 2D Fingerprints for Scaffold Hopping

Abstract

Universities of LeedsMethods. This paper reports a detailed evaluation of the effectiveness of six common types of 2D fingerprint when they are used for scaffold hopping similarity searches of MDDR, WOMBAT and MUV data.Results. The results demonstrate that 2D fingerprints can be used for scaffold hopping, with novel scaffolds being identified in nearly every search that was carried out. The degree of enrichment depends on the structural diversity of the actives that are being sought, with the greatest enrichments often being obtained using ECFP4 fingerprints. Conclusions. 2D fingerprints provide a simple, and computationally efficient, way of identifying novel chemotypes in lead-discovery programmes.

Using Information from Historical High-Throughput Screens to Predict Active Compounds

“…to have a higher scaffold-hopping potential. 36,37 This was confirmed previously for HTS-fingerprint similarity search by Petrone et al 7 Here, we investigated it in the context of machine learning. The diversity of scaffolds was assessed by calculating the distribution of Morgan3 similarities between the training actives and the actives in the first 5% test molecules, as well as by calculating the number of Bemis− Murcko scaffolds (BMS) 9 in the first 5% of the test molecules.…”

Chemoinformatics at the University of Sheffield 2002–2014

“…This characteristic of the coefficient was investigated in a subsequent study by Holliday et al who showed that a related similarity coefficient, the cosine coefficient, was less dependent on the precise nature of the weighing scheme that was being employed and that it was, accordingly, to be preferred if weighted fingerprints were to be used for similarity searching. [25] The weighting-scheme studies summarised here are just one aspect of the work we have conducted on 2D similarity searching over the past decade: other studies have included inter alia an investigation of the extent to which fingerprint-based similarity measures can be used for scaffold-hopping applications, [26] the use of reduced graphs for similarity searching as described further below, similarity searching using Bayesian inference networks, [27] a detailed comparison of the characteristics of different similarity coefficients that can be used with binary fingerprints, [28] and our work on data fusion, as discussed in the next section.…”

Shaping a Screening File for Maximal Lead Discovery Efficiency and Effectiveness: Elimination of Molecular Redundancy

“…60 ECFP4 fingerprints 61 were used for all similarity calculations of compounds. The Tanimoto coefficient 62 was used as the measure of similarity between compounds.…”