Generating three dimensional structures of molecules from the 2D structure is a classic computational chemistry problem. To generate the best possible structure requires quantum mechanical calculations, modelling of solvation, ionisation, tautomerization and then generating an ensemble of conformers. But to generate a starting point, a “best guess given what we know” surely something simpler could be done? The next step down would be a ball-and-spring force field model. Treat all the atoms as balls and bonds as springs, and use classical mechanics to search for the most stable configurations. But still that will take minutes per compound to minimise structures searching all the bond torsions and relaxing the compounds . What about something even simpler, surely from x-ray structures there are some fragments that don’t change much. Enter the high speed rule based methods. If you lived in the US you probably used CONCORD and in Europe CORINA. Blazingly fast and allowing a “best first guess” at the 3D structure of a molecule. Like the electronic equivalent of the molecular building kit they allow chemists to generate sets of 3D structures almost instantly. For high precision work the full QM treatment is still needed, but for a quick look and see or to provide a quick start to QM and Force field minimisation, CORINA and CONCORD are still excellent.
Automatic generation of 3D-atomic coordinates for organic molecules.
Gasteiger, Rudolph, and Sadowski, J., Tetrahedron Computer Methodology(1990) 3, 537–547.
Using CONCORD to construct a large database of three-dimensional coordinates from connection tables
Rusinko, Sheridan, Nilakantan, Haraki, Bauman and Venkataraghavan, . J. Chem. Inf. Model.(1989) 29, 251–255.
#BucketListPapers #DrugDiscovery #MedicinalChemistry #BeTheBestChemistYouCanBe