Scaffold Generator: a Java library implementing molecular scaffold functionalities in the Chemistry Development Kit (CDK)

Abstract

The concept of molecular scaffolds as defining core structures of organic molecules is utilised in many areas of chemistry and cheminformatics, e.g. drug design, chemical classification, or the analysis of high-throughput screening data. Here, we present Scaffold Generator, a comprehensive open library for the generation, handling, and display of molecular scaffolds, scaffold trees and networks. The new library is based on the Chemistry Development Kit (CDK) and highly customisable through multiple settings, e.g. five different structural framework definitions are available. For display of scaffold hierarchies, the open GraphStream Java library is utilised. Performance snapshots with natural products (NP) from the COCONUT (COlleCtion of Open Natural prodUcTs) database and drug molecules from DrugBank are reported. The generation of a scaffold network from more than 450,000 NP can be achieved within a single day.

Database of 4 Million Medicinal Chemistry-Relevant Ring Systems

“…A software for generation of scaffolds and exploration of their hierarchies was released as open source and its application for an analysis of drugs and natural products was described. 17 Recently, Buehler and Reymond analyzed the molecular frameworks in the generated molecular database GDB-13s and compared them with frameworks present in other large molecular collections. 18 The database of existing molecules contains mostly scaffolds with 5-and 6-membered rings connected by linkers, while the GDB-13s contains rings of different sizes and diverse complex ring systems without linker bonds.…”

“…A large majority of these systems (98.6%) were unknown, most of them being macrocycles with fused small rings and synthetically challenging spiro systems. A software for generation of scaffolds and exploration of their hierarchies was released as open source and its application for an analysis of drugs and natural products was described . Recently, Buehler and Reymond analyzed the molecular frameworks in the generated molecular database GDB-13s and compared them with frameworks present in other large molecular collections .…”

MORTAR: a rich client application for in silico molecule fragmentation

“…Fragmentation algorithms can be integrated into or directly developed in MORTAR straightforwardly. Upon release, three algorithms are available: The Ertl algorithm for functional group identification via its open implementation ErtlFunctionalGroupsFinder [ 35 ], the Sugar Removal Utility for glycosidic moiety detection and removal, and Scaffold Generator [ 36 ], a software library for scaffold functionalities, including the scaffold tree dissection into parent scaffolds and an enumerative parent scaffold generation routine for scaffold networks. More functionalities will be added in future releases and with MORTAR being open-source, the software itself can be enhanced or tailored to individual needs.…”