Visualization and Virtual Screening of the Chemical Universe Database GDB-17

Abstract

The chemical universe database GDB-17 contains 166.4 billion molecules of up to 17 atoms of C, N, O, S, and halogens obeying rules for chemical stability, synthetic feasibility, and medicinal chemistry. GDB-17 was analyzed using 42 integer value descriptors of molecular structure which we term "Molecular Quantum Numbers" (MQN). Principal component analysis and representation of the (PC1, PC2)-plane provided a graphical overview of the GDB-17 chemical space. Rapid ligand-based virtual screening (LBVS) of GDB-17 using the city-block distance CBD(MQN) as a similarity search measure was enabled by a hashed MQN-fingerprint. LBVS of the entire GDB-17 and of selected subsets identified shape similar, scaffold hopping analogs (ROCS > 1.6 and T(SF) < 0.5) of 15 drugs. Over 97% of these analogs occurred within CBD(MQN) ≤ 12 from each drug, a constraint which might help focus advanced virtual screening. An MQN-searchable 50 million subset of GDB-17 is publicly available at www.gdb.unibe.ch .

Expanding the fragrance chemical space for virtual screening

“…Nearest neighbour searching by city-block distance in MQN-space can be carried out extremely fast even in extremely large databases when these are pre-organized by the sum of all MQN-values as hash-function [57]. A series of web-based MQN-browser applications are freely accessible at http://www.gdb.unibe.ch to perform such searches in various public databases by MQN-similarity [58].…”

“…Nearest neighbours searches were performed for 13 different classical fragrance molecules falling in the size-range of GDB-13, which are mostly monoterpenes (Table 3 and Additional file 4). The distance boundary CBD MQN  ≤ 12 was used because it was found to narrow the search to useful bioactive analogs in previous virtual screening studies [57]. A further limitation to isomers within the preset CBD MQN distance boundary was also considered because isomerism further constrains the functional group and molecular size similarity, which are very important parameters in fragrance molecule properties.…”

“…This browser was programmed as previously described for the MQN-browser for other databases to allow nearest neighbour searching of any query molecules within the FL-subsets using CBD MQN as similarity measure [57]. Searching in database space is enabled by use of bit mask values to store the database information of the structures.…”

Advanced Multidimensional Separations in Mass Spectrometry: Navigating the Big Data Deluge

“…While enumeration of all possible molecular structures is impossible, some recent progress has been made towards enumerating compounds of 17 atoms or less containing C, H, N, O, S, and halogens, which has resulted in 166.4 billion virtual drug-like compounds of ca. 350 Da or less (39,40). Such new compound discovery and annotation efforts are big data challenges which represent the chemical sciences in the purest sense, and form the basis for the nascent fields of chemography (41) and cheminformatics (42,43).…”

Building Compound Archives for the Future

“…While this may seem a large number, it has to be seen in the context of the potential size of the chemical universe. Reymond et al [3] have shown that enumerating all the sensible possibilities for compounds with up to 17 heavy atoms leads to 10 11 structures, and even that is probably conservative. DNA-encoded libraries can reach sizes of 10 8 but even here we are sampling at a rate of 1 in 1000, with a restricted number of assembly reactions.…”