ChemGPS-NP – tuned for navigation in biologically relevant chemical space

Natural compounds have a unique chemical diversity occupying a different and larger space than that normally dealt with in medicinal chemistry [1, 2]. They are evolutionary selected and pre-validated by Nature with explicit biological activities, making them highly interesting for development of new drug lead candidates.

Chemical space is a multi-dimensional region defined by the descriptors chosen to describe a set of chemical compounds [3]. Of utmost importance for discovery of new active compounds for future therapies is the identification and charting of a biologically relevant chemical space and a primary key to this is the coverage of the diverse natural product chemical space [1, 2, 4].

A map of chemical space can be constructed by applying the same principles as the Mercator convention in geography. Rules are corresponding to dimensions (e.g. longitude and latitude), and structures are corresponding to objects (e.g. cities and countries) [5]. The rules and objects together present the chemical space map, where the coordinates are t-scores from principal component analysis [6].

Here we present ChemGPS-NP, a new tool tuned for exploration of biologically relevant natural products chemical space, forming a framework for making compound comparison and selection more effective and increasing probability of hit generation when screening the vast diversity of natural products in the search for novel bioactive molecules.

References: 1. Larsson J. et al. (2005), J. Nat. Prod. 68: 985–991. 2. Feher, M., Schmidt, J.M. (2003), J. Chem. Inf. Comput. Sci. 43: 218–227. 3. Dobson, C.M. (2004), Nature 432: 824–828. 4. Koch, M.A. et al. (2005), Proc. Natl. Acad. Sci. USA 102: 17272–17277. 5. Oprea, T.I., Gottfries, J. (2001), J. Comb. Chem. 3: 157–166. 6. Jackson, J.E. (1991), A users guide to principal components, Wiley, New York.