Investigating Pharmacological Similarity by Charting Chemical Space.
In this study, biologically relevant areas of the chemical space were analyzed using ChemGPS-NP. This application enables comparing groups of ligands within a multidimensional space based on principle components derived from physicochemical descriptors. Also, 3D visualization of the ChemGPS-NP global map can be used to conveniently evaluate bioactive compound similarity and visually distinguish between different types or groups of compounds. To further establish ChemGPS-NP as a method to accurately represent the chemical space, a comparison with structure-based fingerprint has been performed. Interesting complementarities between the two descriptions of molecules were observed. It has been shown that the accuracy of describing molecules with physicochemical descriptors like in ChemGPS-NP is similar to the accuracy of structural fingerprints in retrieving bioactive molecules. Lastly, pharmacological similarity of structurally diverse compounds has been investigated in ChemGPS-NP space. These results further strengthen the case of using ChemGPS-NP as a tool to explore and visualize chemical space.
Chemistry Innovation Centre, Discovery Sciences, AstraZeneca R&D Mölndal , SE-43183 Mölndal, Sweden.
Rosa
R
Buonfiglio
Chemistry Innovation Centre, Discovery Sciences, AstraZeneca R&D Mölndal , SE-43183 Mölndal, Sweden.
Ola
O
Engkvist
Chemistry Innovation Centre, Discovery Sciences, AstraZeneca R&D Mölndal , SE-43183 Mölndal, Sweden.
Péter
P
Várkonyi
Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University , BMC box 574, S-751 23 Uppsala, Sweden.
Astrid
A
Henz
Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University , BMC box 574, S-751 23 Uppsala, Sweden.
Elisabet
E
Vikeved
Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University , BMC box 574, S-751 23 Uppsala, Sweden.
Anders
A
Backlund
Chemistry Innovation Centre, Discovery Sciences, AstraZeneca R&D Mölndal , SE-43183 Mölndal, Sweden.
Thierry
T
Kogej
D017076:Computer-Aided Design; D062313:Databases, Pharmaceutical; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D012984:Software; D013329:Structure-Activity Relationship
D008024:Ligands