Small molecules interaction screens

The fast growing amount of molecular information related to small molecule interactions with biological systems, generated in both academic and industrial screening centers, requires the design of molecular information systems which integrate bio- and chemoinformatics... 

Fig. 7.1. Different yeast n-hybrid systems that have been developed to study protein-protein, protein-DNA, protein-RNA, and protein - small molecule interactions. A. In the original version of the Y2H system, transcriptional activation of the reporter gene is reconstituted by recruitment of the activation domain (AD) to the promoter region through direct interaction of protein X and Y, since protein X is fused to a DNA-binding domain (DBD) and protein Y is fused to the AD [1], B. In the Y1 H assay, the AD is fused directly to the DBD [109]. This assay can be used to screen either DBDs that can bind to a specific DNA sequence or the in vivo binding site for a given DBD. C.

Fletcher, S., and Hamilton, A. D. (2007) Protein-protein interaction inhibitors Small molecules from screening techniques. Curr. Topics Med. Chem. 7, 922-927. 

Cash, K. Ricci, F. Plaxco, K. A. A general electrochemical method for label-free screening of protein-small molecule interactions. Chem. Commun. 2009, 41, 6222-6224. 

Ross A, Schlotterbeck G, Klaus W et al (2000) Automation of NMR measurements and data evaluation for systematically screening interactions of small molecules with target proteins. JBiomol NMR 16 139-146... 

Chapman RL, Stanley TB, Hazen R, Garvey EP. Small molecule modulators of HIV Rev/Rev response element interaction identified by random screening. Antiviral Res 2002 54 149-62. 

Accounting for electron correlation in a second step, via the mixing of a limited number of Slater determinants in the total wave function. Electron correlation is very important for correct treatment of interelectronic interactions and for a quantitative description of covalence effects and of the structure of multielec-tronic states. Accounting completely for the total electronic correlation is computationally extremely difficult, and is only possible for very small molecules, within a limited basis set. Formally, electron correlation can be divided into static, when all Slater determinants corresponding to all possible electron populations of frontier orbitals are considered, and dynamic correlation, which takes into account the effects of dynamical screening of interelectron interaction. 

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