Structure Oriented Design

Structure oriented design refers to projects aimed at the creation of molecules with unusual structural characteristics not necessarily related to some useful property. This brings to mind a plethora of classical studies such as the previously discussed syntheses of cyclooctatetraene, Dewar benzene, or asterane. More recent examples include the syntheses of the dodecahedrane and tetrahedrane frameworks. The goal of the investigations in this area is first to invent and then to synthesize certain non-trivial molecules having unique structural features. This uniqueness very often refers to a novelty in the general shape of the molecules (as for dodecahedrane or catenanes), which are otherwise constructed in accordance with the classical concepts of structural theory. At the same time, quite a number of unprecedented structures have... 

It would not be very difficult to continue with a list of impressive results published in the area of structure-oriented design. We believe, however, that at least some of the general tendencies and ramifications can be seen in the examples given above. 

The idea is to gain the benefits of 00, but without throwing away old code. You want to be able to make systems that remain flexible as your organization and its structure and working methods change. You want to build many applications from a set of basic components. These are features of object-oriented designs. 

There has been considerable discussion on the validity of docking and scoring functions in structure-based design because of the complex issues involved such as ligand orientation, water participation, or flexibility of the target protein itself [186-190]. 

Peptide libraries made up of millions of randomized peptide sequences have proven useful for the identification of novel ligands that may be of interest for the development of medicinally active compounds.[123,124] However, due to the short length of the individual peptides in linear peptide libraries, they possess considerable conformational flexibility and can populate multiple random-like conformations. This flexibility does not allow one to determine the precise three-dimensional orientation of the side chains, which greatly impedes structure-based design. These facts have greatly accelerated studies into conformationally restricted libraries, where constraints have been introduced to decrease peptide flexibility. However, what is really required is the design of conformationally defined and constrained templates for library display. These templates present the side chains of selected residues in a defined three-dimensional space. Thus, as an alternative to linear peptide libraries, the well-char-... 

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