Evolutionary de novo design

Lonally, the templates were chosen by trial and error or exhaustive enumeration. A itafional method named ZEBEDDE (ZEolites By Evolutionary De novo DEsign) en developed to try to introduce some rationale into the selection of templates et al. 1996 Willock et al. 1997]. The templates are grown within the zeolite by an iterative inside-out approach, starting from a seed molecule. At each jn an action is randomly selected from a list that includes the addition of new (from a library of fragments), random translation or rotation, random bond rota-ing formation or energy minimisation of the template. A cost function based on erlap of van der Waals spheres is used to control the growth of the template ale ... 

Schneider, G., Clement-Chomienne, O., Hilfiger, L, Schneider, P., Kirsch, S., Bohm, H., and Neidhart, W. Virtual screening for bioactive molecules by evolutionary de novo design. Angew. Chem., Int. Ed. 2000, 39, 4130-4133. 

Rogers-Evans M, Alanine Al, Bleicher KH et al (2004) Identification of novel cannabinoid receptor ligands via evolutionary de novo design and rapid parallel synthesis. QSAR Comb Sci 23 426-430... 

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. 

Figure 7.9 Non-deterministic de novo design pipeline including an evolutionary algorithm for optimization. This scheme contains a population-based algorithm that mimicks biological evolution through mutation and recombination during the breeding process.

GAs or other methods from evolutionary computation are applied in various fields of chemistry Its tasks include the geometry optimization of conformations of small molecules, the elaboration of models for the prediction of properties or biological activities, the design of molecules de novo, the analysis of the interaction of proteins and their ligands, or the selection of descriptors [18]. The last application is explained briefly in Section 9.7.6. 

Nicolaou, C. A., Apostolakis, J., Pattichis, C. S. (2009) De novo drug design using multiobjective evolutionary graphs. J Chem Inf Model 49,295-307. 

In the adult human, lysine is an essential amino acid. It cannot be synthesized de novo from non-protein sources. In the child, both arginine and lysine are essential since there is a need for more arginine than can be supplied by endogenous routes. The combination of trypsin and carboxypeptidase B seems to be a convenient evolutionary device to ensure an adequate supply of these amino acids from dietary protein. Similarly, the other essential amino acids listed in Table II are those most likely to arise from the combined action of pepsin and chymotrypsin followed by carboxypeptidase A. Hence, the overall proteolytic apparatus is apparently designed to meet the nutritional needs of man for essential amino acids. 

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