understanding and classifying metabolite space and metabolite-likeness理解和分类代谢物空间和metabolite-likeness.pdfVIP

Understanding and Classifying Metabolite Space and Metabolite-Likeness 1,2,3 2,3 1,3 4 2,3 Julio E. Peironcely , Theo Reijmers , Leon Coulier , Andreas Bender *, Thomas Hankemeier * 1TNO Research Group Quality and Safety, Zeist, The Netherlands, 2 Division of Analytical Biosciences, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden, The Netherlands, 3 Netherlands Metabolomics Centre, Leiden, The Netherlands, 4 Unilever Centre for Molecular Science Informatics, Department of Chemistry, University of Cambridge, Cambridge, United Kingdom Abstract While the entirety of ‘Chemical Space’ is huge (and assumed to contain between 1063 and 10200 ‘small molecules’), distinct subsets of this space can nonetheless be defined according to certain structural parameters. An example of such a subspace is the chemical space spanned by endogenous metabolites, defined as ‘naturally occurring’ products of an organisms’ metabolism. In order to understand this part of chemical space in more detail, we analyzed the chemical space populated by human metabolites in two ways. Firstly, in order to understand metabolite space better, we performed Principal Component Analysis (PCA), hierarchical clustering and scaffold analysis of metabolites and non-metabolites in order to analyze which chemical features are characteristic for both classes of compounds. Here we found that heteroatom (both oxygen and nitrogen) content, as well as the presence of particular ring systems was able to distinguish both groups of compounds. Secondly, we established which molecular descriptors and classifiers are capable of distinguishing metabolites from non-metabolites, by assig