Structure-based approaches

Figure 15.2 Historical progress of ligand structure-based approaches from substructure search to analysis of 3-dimensional molecular interaction fields.

The practical utility of the target-structure-based approach in the design of chemical libraries is still limited because of the requirement of quality crystallographic data, detailed knowledge of the ligand binding mode, and... 

Waszkowycz B. Structure-based approaches to drug design and virtual screening. Curr Opin Drug Discov Dev 2002 5 407-13. 

Iwata Y, Arisawa M, Hamada R, Kita Y, Mizutani MY, Tomioka N, Itai A, Miyamoto S. Discovery of novel aldose reductase inhibitors using a protein structure-based approach 3D-database search followed by design and synthesis. J Med Chem 2001 44 1718-28. 

For both nonspecific and structure-based approaches, physicochemical solvation parameters may be used directly, or they may be embedded in quantitative structure-activity relationships.3 This chapter starts with a review of the thermodynamic equations that may be used for a quantitative description of the free energy of solutes in fluid media. Then it provides an... 

Ruscio, J., St Ruscio, A. M. (2002). A structure-based approach to psychological measurement Matching measurement models to latent structure. Assessment, 9, 4-16. 

A structure-based approach for discovering protein ligands and for drug design by coupling size exclusion chromatography, mass spectrometry, and nuclear magnetic resonance spectroscopy. Anal. Chem. 2001, 73, 571-581. 

It is furthermore noted that the TTC concepts, including the structure-based approaches, are derived from databases covering substances used as direct and indirect food additives, pesticides, and industrial chemicals, and cover toxic effects related to systemic exposure to these chemicals. In addition, it is underlined that TTC has not been developed for endpoints associated with direct contact such as irritation or sensitization. 

Skolnick J, BryKnski M (2009) FINDSITE a combined evolution/structure-based approach to protein function prediction. Brief Bioinform 10 378-391... 

Thai, K.-M. and Ecker, G.E. (2007) Predictive models for hERG channel blockers ligand-based and structure-based approaches. Current Medicinal Chemistry, 14, 3003-3026. 

The advent of more accurate and rapid tools in chemoin-formatics and virtual screening makes it possible to design and synthesize a small subset of representative compounds (focused library) of a larger library. Out of various improved methods these two diversity- or structure-based approaches are frequently exercised in the design of a focused library. Once the 3D coordinates of a protein target are determined by either X-ray crystal structures or NMR, a structure-based library design is a more productive and viable approach. 

Billions of dollars are spent in the United States alone on symptomatic relief from this disease. The ubiquitousness of this disease has led many people to seek a cure for many years (the discovery of the class of HRV inhibitors described here is over 20 years old). This chapter will describe the influence of structure-based approaches in the design of a class of antipicornaviral agents called capsid-binding inhibitors. 

Fattorusso, R., et al., Discovery of a novel class of reversible non-peptide caspase inhibitors via a structure-based approach. J Med Chem, 2005,48, 1649-1656. 

Sherman W., Using fragments to couple ligand- and structure-based approaches. Presented at the ACS Meeting, Boston, MA, 18-23 August 2007. 

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