Molecule-protein interactions

Hermkens, P.H.H. and Muller, G., The impact of combinatorial chemistry on drug discovery, in Ernst Schering Research Foundation Workshop Small Molecule-Protein Interactions, Vol. 42, 2003, pp. 201-220. 

Stahl, M. and Schulz-Gasch, T. Practical database screening with docking tools. In Small Molecule-Protein Interaction, Waldmann, H. and Koppitz, M. (Eds.). Springer-Verlag, Berlin and Heidelberg, 2003, 127-150. 

A number of useful reviews of small molecule-protein interaction have appeared (D2, E4, S26, W7), and these contain detailed treatments of the mathematical analysis of binding data as well as information on experimental methods. 

Functional protein microarrays are useful for direct analysis of biochemical activity (e.g., substrate specificity, Refs. 98 and 99), protein protein interaction (100), or small molecule protein interaction. Proteins of interest are over expressed and applied in pure form on addressable arrays, and assays performed (101). 

Lumry, R. (1979) Dynamical aspect of a small molecule protein interaction, in Briabanti, A, (eds.) Bioenergetics and thermodynamics, NATO Advanced Study, Parma, Italy, pp. 435-454. 

Compared with the Y2H system, the Y3H system used to detect RNA-protein interactions has one additional component, a hybrid RNA molecule [90], One half of the hybrid RNA is a known RNA (R) that can binds the MS2 coat protein (MS2) with high affinity and serves as an anchor. The other half is RNAX, whose interaction with protein Y is being tested. D. Another version of the Y3H system can be used to detect small molecule-protein interactions [96], Ligand LI which interacts with protein X can be linked to ligand L2, and thus, if L2 interacts with Y, transcriptional activation of the reporter gene will be reconstituted. 

Baker K, Sengupta D, Salazar-Jimenez G, Cornish VW. An optimized dexamethasone-methotrexate yeast 3-hybrid system for high-throughput screening of small molecule-protein interactions. 

Caligiuri M, Molz L, Liu Q, Kaplan F, Xu JP, Majeti JZ, Ramos-Kelsey R, Murthi K, Lievens S, Tavernier J, Kley N. MASPIT three-hybrid trap for quantitative proteome fingerprinting of small molecule-protein interactions in mammalian cells. Chem. Biol. 2006 13 711-722. 

CHEMICAL BIOLOGY BASED ON SMALL MOLECULE-PROTEIN INTERACTION... 

In addition, protein chip arrays can be multifaceted by changing the capture ligand on the protein chip surface. For example, small molecule array is used to investigate smaU-molecule-protein interaction, AB array uses specific antibody as the capture ligand to study cellsignaling, and peptide array uses peptides as capture ligands to study protein—protein interaction. 

Since the conception of the two-hybrid assay to detect protein-protein interactions in vivo at the end of the 1980s, key modifications to this assay have expanded its scope to detect DNA-, RNA-, and small molecule-protein interactions in so-called n-hybrid assays. More recently, n-hybrid assays have also been used to detect enzyme catalysis, where enzyme activity is linked to cell survival via transcription of a reporter gene. Here we look at the initial publications that moved the two-hybrid assay into each of these new directions. 

T. Willson, Chemical genomics of orphan nuclear receptors, in Ernst Sobering Research Foundation Workshop 42 Small Molecule-Protein Interactions, (Eds. H. Waldmann, M. Koppitz), Springer, Berlin, 2003, pp. 29-42. 

The yeast three-hybrid (Y3H) system is a cellular assay system designed for the identification and characterization of small molecule-protein interactions in intact cells [25]. It uses yeast Saccharomyces cerevisiae as a host system and combines aspects of the yeast two-hybrid (Y2H) system [26] with recent developments in chemical dimerizer technology [27, 28],... 

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