Atom-Atom-Path similarity and Sphere Exclusion clustering: tools for prioritizing fragment hits.

ABSTRACT:

Background

After performing a fragment based screen the resulting hits need to be prioritized for follow-up structure elucidation and chemistry. This paper describes a new similarity metric, Atom-Atom-Path (AAP) similarity that is used in conjunction with the Directed Sphere Exclusion (DISE) clustering method to effectively organize and prioritize the fragment hits. The AAP similarity rewards common substructures and recognizes minimal structure differences. The DISE method is order-dependent and can be used to enrich fragments with properties of interest in the first clusters.

Results

The merit of the software is demonstrated by its application to the MAP4K4 fragment screening hits using ligand efficiency (LE) as quality measure. The first clusters contain the hits with the

SUBMITTER: Gobbi A 

PROVIDER: S-EPMC4392110 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature