Computational de novo design

E.-W. Lameijer, R.A. Tromp, R.F. Spanjersberg, J. Brussee and A.P. IJzerman, Designing active template molecules by combining computational de novo design and human chemists expertise, J. Med. Chem., 50, 1925-1932 (2007). 

Cochran EV, Wu SP, Wang W, Nanda V, Saven JG, Therien MJ, DeGrado WE. Computational de novo design and characterization of a four-heUx bundle protein that selectively binds a nonbiological cofactor. J. Am. Chem Soc. 2005 127 1346-1347. 

Role of 3D-QSAR in 3D Database Searching, Combinatorial Library Design, and Computer De Novo Design... 

Some aspects, such as the computer representation and manipulation of proteins and nucleic acids, could not be covered. Even the modeling of the interactions of small molecules with proteins, as dealt with in docking software or software for de novo design could not be included in the Textbook, although chapters in the Handbook do treat these subjects. 

The computational chemists were able to form collaborations with their fellow physical chemists. Some of the research questions dealt with molecular conformation and spectroscopy. The 1970s were full of small successes such as finding correlations between calculated and experimental properties. Some of these correlations were published. Even something so grand as the de novo design of a pharmaceutical was attempted but was somewhat beyond reach. 

As the availability of crystal structures increased in the early 1990s, a number of experimental and computational methods were developed to use the structure of the protein target as a route to discover novel hit compounds. The methods include de novo design, virtual screening, and fragment-based discovery. These developments are covered in more detail in the later chapters of this book, but their main features can be summarized as follows. 

Bohm HJ. The computer program LUDI a new method for the de novo design of enzyme inhibitors. J Comput Aided Mol Design 1992 6 61-78. 

De novo design approaches computationally generate virtual molecules based on protein active sites or simply just de noco-designed molecules [39]. 

Schneider G, Fechner U. Computer-based de novo design of drug-like molecules, Nature Reviews Drug Discovery 4 649-663 (2005). 

Schneider, G., Lee, M.L., Stahl, M., and Schneider, G. De novo design of molecular architectures by evolutionary assembly of dmg-derived building blocks./. Comput.-Aided Mol. Des. 2000, 34, 487-494. 

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