Rational-based design

O. K. Scheible, Development of a rationally based design protocol for the ultraviolet light disinfection process. Journal WPCE 59, 25-31 (1987). 

The technical importance of the majority of the discussed enzymes surely motivates "surgery" of the outlin nature aiming at alteration of the functional properties. The well explor protein engineering approach of em e hybrid formation had earlier largely addressed the thermal stability. We have here summarized evidence that justifies further attempts to engineer enzymatic properties applying this as well as more rationally based design procedures. 

A topic of actuality is the study of receptor proteins and enzymes for which data bases with crystallographic information are now made available. Computer modelling of the active sites of receptors and enzymes are important tools in rational drug design. Principal components and cluster analysis can be applied to the primary... 

In this chapter, however, our objective is more restricted. We will purposely choose simple cases and make simplifying assumptions such that the results are PID controllers. We will see how the method helps us select controller gains based on process parameters (/. e., the process model). The method provides us with a more rational controller design than the empirical tuning relations. Since the result depends on the process model, this method is what we considered a model-based design. 

Tanaka K, Miura T, Umezawa N, Urano Y, Kikuchi K, Higuchi T, Nagano T (2001) Rational design of fluorescein-based fluorescence probes. Mechanism-based design of a maximum fluorescence probe for singlet oxygen. J Am Chem Soc 123 2530-2536... 

Initially, most theoretical methods calculated the properties of molecules in the gas phase as isolated species, but chemical reactions are most often carried out in solution. Biochemical reactions normally take place in water. Consequently, there is increasing interest in methods for including solvents in the calculations. In the simplest approach, solvents are treated as a continuum, whose average properties are included in the calculation. Explicit inclusion of solvent molecules in the calculation greatly expands the size of the problem, but newer approaches do this for at least those solvent molecules next to the dissolved species of interest. The detailed structures and properties of these solvent molecules affect their direct interaction with the dissolved species. Reactions at catalytic surfaces present an additional challenge, as the theoretical techniques must be able to handle the reactants and the atoms in the surface, as well as possible solvent species. The first concrete examples of computationally based rational catalyst design have begun to appear in publications and to have impact in industry. 

The above achievements depend highly on both the recent advances in rational catalyst design with the aid of computational science represented by DFT calculations and the wide range of catalyst design possibilities that are afforded by FI catalysts. These possibilities are derived from the readily varied steric and electronic properties of the phenoxy-imine ligands. It is expected that future research on FI catalysts will provide opportunities to produce additional polyolefin-based materials with unique microstructures and a chance to study catalysis and mechanisms for olefin polymerization. 

Funatsu K. Miyao T. Arakawa M. Systematic generation of chemical structures for rational drug design based on QSAR models. Current Computer-Aided Drug Design, 2011, 7 (1), 1-9. 

Exploiting Ligand and Receptor Adaptability in Rational Drug Design Using Dynamics and Structure-Based Strategies... 

E., and Mandine, E. SAR and X-ray -a new approach combining fragment-based screening and rational drug design application to the discovery of nanomolar inhibitors of src SH2. 

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