Computational characterization of SAR microenvironments in high-throughput screening data
Mathias Wawer*, Su Sun*, Jürgen Bajorath
Department of Life Science Informatics, Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany; *These authors have contributed equally to this work.
Purpose: A computational approach is described to analyze structure–activity relationship (SAR) information contained in compound and screening data sets. The methodology is designed to explore SAR information in a systematic and compound-centric manner in order to aid in the selection of hits from high-throughput screening (HTS) data.
Methods: Chemical neighborhood graphs integrate a graphical representation of the chemical environment of each active compound in a data set with the potency distribution within its neighborhood and information from a quantitative SAR analysis function. Environments are systematically generated and ranked by SAR information content. From these environments, key compounds and compound series can be selected.
Results: The methodology is described in detail. In addition, the application to four screening data sets is reported, revealing different SAR characteristics. A number of different examples of compound environments are presented and discussed that have varying SAR information content.
Conclusion: Chemical neighborhood graphs provide an intuitive graphical access to SAR information contained in hit sets. SAR information is analyzed in a compound-centric manner, with a focus on local SAR environments (microenvironments). It is anticipated that this approach will complement and help to further refine current hit selection strategies and trigger the development of additional graphical analysis methods to search for SAR information in HTS data.
Keywords: screening data sets, hit selection, computational analysis, graphical representation, structure–activity relationship information
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF]
Readers of this article also read:
Prozorova GF, Pozdnyakov AS, Kuznetsova NP, Korzhova SA, Emel’yanov AI, Ermakova TG, Fadeeva TV, Sosedova LM
Published Date: 16 April 2014
Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects [Corrigendum]
Cui Y, Song Y, Wang J, Yu Z, Schuster A, Barrett YC, Frost C
Published Date: 27 March 2014
Pharmacokinetics and pharmacodynamics of acetylsalicylic acid after intravenous and oral administration to healthy volunteers
Nagelschmitz J, Blunck M, Kraetzschmar J, Ludwig M, Wensing G, Hohlfeld T
Published Date: 19 March 2014
Gao B, Doan A, Hybertson BM
Published Date: 3 February 2014
Ashwanikumar N, Kumar NA, Nair SA, Kumar GS
Published Date: 15 November 2012
A novel preparation method for silicone oil nanoemulsions and its application for coating hair with silicone
Hu Z, Liao M, Chen Y, Cai Y, Meng L, Liu Y, Lv N, Liu Z, Yuan W
Published Date: 12 November 2012
Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS
Published Date: 27 July 2012
Particle size reduction to the nanometer range: a promising approach to improve buccal absorption of poorly water-soluble drugs
Rao S, Song Y, Peddie F, Evans AM
Published Date: 20 June 2011
Pitipol Choopong, Nattaporn Tesavibul, Nattawut Rodanant
Published Date: 14 July 2010
Characterization of complexation of poly (N-isopropylacrylamide-co-2-(dimethylamino) ethyl methacrylate) thermoresponsive cationic nanogels with salmon sperm DNA
Jim Moselhy, Tasnim Vira, Fei-Fei Liu, et al
Published Date: 24 August 2009