Virtual receptor sites

With the exception of the research of Yoehida et al. (26) whioh represents the coalition of two ideas, that is the elucidation of the mode of action of (+)-ABA relative to receptor sites and production of practical analogs of (+)-ABA for possible agricultural use, virtually all endeavors concerning (+)-ABA have been ocnoemed only with the possible mode of action of (+)-ABA. Thus, all of the structures that we have just examined have primarily been evaliiated to determine their relative role in (+)-ABA formation and metabolism. This in no way detracts frcm the difficult and elegant oheadstry that has been carried out. 

For many protein drug targets crystal or solution structures are not available. In such cases homology models (130,131)and pseudoreceptor models (132) are often used. However, unless there is a very high conservation of receptor site residues the use of homology models for virtual screening is much riskier than using solved structures. On the other hand, the PDB contains a wealth of protein... 

The protein has to be prepared only once for a virtual screening experiment unless different protein conformations are considered. The receptor site needs to be determined and charges have to be assigned. The protein structure and the receptor site have to be modeled as accurately as possible. Determining protein surface atoms and site points as well as the assignment of interaction data, such as... 

Evers, A. Klebe, G. Ligand-supported homology modelling of G-protein-coupled receptor sites models sufficient for successful virtual screening. Angew. Chem. Int. Ed. 2004, 43 (2), 248-251. 

Five pharmacophore point types are used to generate PDT fingerprints hydrogen-bond acceptor atom, hydrogen-bond donor atom, acceptor site, donor site, and hydrophobic center. While donor and acceptor atoms are part of the molecule, site points refer to interaction points located on a virtual receptor defined by geometrical criteria [Martin, Bures et al., 1993]. Interfeature distances from 2.5 to 15.0 A are divided into 27 distance bins of equal width (i.e.,... 

SAR of DES. One may consider DES as another form of estradiol wherein the two 6-membered rings B and C open up and a 6-membered aromatic ring D introduced in place of the cyclopentane ring. It was further suggested that the aetual distance prevailing between the two DES phenol OH moieties was virtually the same as the C-3 OH to C-17 OH distance existing in estradiol and, hence, these two entities may prove to be a perfect fit to the same receptor site. Recently, with the advent of latest computer softwares the medicinal chemist has established the distance between the two OH moieties in DES to be 12.lA and in estradiol 10.9A. 

Atropine competes with ACh and other muscarinic agonisu for a common binding site on the muscarinic receptor, thus effectively antagonizing the actions of ACh at muscarinic receptor sites, which leads to increased tracheobronchial and salivary secretions, hronchoconstriclion, and bradycardia. The usefulness of atropine is virtually undisputed. 

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