Drug structure-based

Thus there is a distinction between ligand- and structure-based drug design, which are described in more detail in Sections 10.4.6.1 and 10.4.6.2. 

Figure 10.4-5. Different strategies to design a ligand in structure-based drug design docking (left), building (center), and linking (right),...

Kubinyi H1998. Structure-based Design of Enzyme Inhibitors and Receptor Ligands. Current Opinion i. Drug Discovery and Development 1 5-15. 

Kuntz I D 1992. Structure-Based Strategies for Drug Design and Discovery. Science 257 1078-1082. 

In general the relevance of predictions of structure-function relationships based on molecular modeling and structural bioinformatics are threefold. First they can be used to answer the question of which partners (proteins) could interact. Second, predictions generate new hypotheses about binding site, about molecular mechanisms of activation and interaction between two partners, and can lead to new ideas for pharmacological intervention. The third aim is to use the predictions for structure-based drug design. 

While there is a vast range of different drug structures, there are only a relatively small number of chemical reactions, some of which are shown below in Table 5.13 (p. 199), involved in the production of metabolites. Based on the structure of the drug, it is therefore possible to predict the most likely metabolites. Use may then be made of reconstructed ion chromatograms (RlCs) of mlz values corresponding to the predicted molecular weights of these metabolites to locate them within the LC-MS data obtained. 

X-Ray Crystallographic Analysis and Structure-Based Drug Design. 32... 

Also in the 1980s, structure-based drug design (SBDD) underwent a similar cycle. Early proponents oversold what could be achieved through SBDD, thereby causing pharmaceutical companies to reconsider their investments when they discovered that SBDD too was no panacea for filling the drug discovery cornucopia with choice molecules for development. Nevertheless, SBDD was an important advance. 

This chapter consists of four main sections. The first provides an overall description of the process of contemporary protein structure determination by X-ray crystallography and summarizes the current computational requirements. This is followed by a summary and examples of the use of structure-based methods in drug discovery. The third section reviews the key developments in computer hardware and computational methods that have supported the development and application of X-ray crystallography over the past forty or so years. The final section outlines the areas in which improved... 

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