Template-based combinatorial enumeration of virtual compound libraries for lipids

Manish Sud,Shankar Subramaniam,Eoin Fahy

doi:10.1186/1758-2946-4-23

Abstract

A variety of software packages are available for the combinatorial enumeration of virtual libraries for small molecules, starting from specifications of core scaffolds with attachments points and lists of R-groups as SMILES or SD files. Although SD files include atomic coordinates for core scaffolds and R-groups, it is not possible to control 2-dimensional (2D) layout of the enumerated structures generated for virtual compound libraries because different packages generate different 2D representations for the same structure. We have developed a software package called LipidMapsTools for the template-based combinatorial enumeration of virtual compound libraries for lipids. Virtual libraries are enumerated for the specified lipid abbreviations using matching lists of pre-defined templates and chain abbreviations, instead of core scaffolds and lists of R-groups provided by the user. 2D structures of the enumerated lipids are drawn in a specific and consistent fashion adhering to the framework for representing lipid structures proposed by the LIPID MAPS consortium. LipidMapsTools is lightweight, relatively fast and contains no external dependencies. It is an open source package and freely available under the terms of the modified BSD license.

Highlights

IntroductionIntroduction to methodology and encoding rulesJ Am Chem Soc 1988, 28:31–36. 27. Weininger D, Weininger A, Weininger JL, SMILES. 2: Algorithm for generation of unique SMILES notation
Introduction to methodology and encoding rulesJ Am Chem Soc 1988, 28:31–36. 27
Virtual libraries are enumerated for the specified lipid abbreviations using matching lists of pre-defined templates and chain abbreviations, instead of core scaffolds, linkers and lists of Rgroups provided by the user as SMILES or SD files. 2D structures of the enumerated lipids are drawn in a specific fashion; their representation is consistent and adheres to the framework for representing lipid structures proposed by LIPID MAPS consortium [29,30]

Summary

Introduction

Introduction to methodology and encoding rulesJ Am Chem Soc 1988, 28:31–36. 27. Weininger D, Weininger A, Weininger JL, SMILES. 2: Algorithm for generation of unique SMILES notation. A variety of software packages are available for the combinatorial enumeration of virtual compound libraries. All possible structures are enumerated by the combinatorial attachment of Rgroups to the core scaffold along with the placement of any linkers between them and a virtual compound library is generated as a SMILES or SD file. Input SD files contain 2D atomic coordinate information for core scaffolds and R-groups, it is not possible to specify the exact orientation of R-groups around scaffolds for the structures enumerated for virtual libraries in any available software package, to the best of our knowledge. Different software packages end up generating completely different orientations of R-groups around scaffolds due to different internal strategies deployed for their optimal placement in the enumerated structures. 2D structure layouts for the enumerated structures are not always consistent across software packages

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