Similarity search profiles as a diagnostic tool for the analysis of virtual screening calculations.
An analysis method termed similarity search profiling has been developed to evaluate fingerprint-based virtual screening calculations. The analysis is based on systematic similarity search calculations using multiple template compounds over the entire value range of a similarity coefficient. In graphical representations, numbers of correctly identified hits and other detected database compounds are separately monitored. The resulting profiles make it possible to determine whether a virtual screening trial can in principle succeed for a given compound class, search tool, similarity metric, and selection criterion. As a test case, we have analyzed virtual screening calculations using a recently designed fingerprint on 23 different biological activity classes in a compound source database containing approximately 1.3 million molecules. Based on our predefined selection criteria, we found that virtual screening analysis was successful for 19 of 23 compound classes. Profile analysis also makes it possible to determine compound class-specific similarity threshold values for similarity searching.
Xue
Ling
L
Department of Computer-Aided Drug Discovery, Albany Molecular Research, Inc. (AMRI), AMRI Bothell Research Center (AMRI-BRC), 18804 North Creek Parkway, Bothell, Washington 98011-8012, USA.
Godden
Jeffrey W
JW
Stahura
Florence L
FL
Bajorath
Jürgen
J
D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical / Q000706:statistics & numerical data*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014584:User-Computer Interface