Molecular modeling systematic search

Tel. 415-903-3900, fax 415-961-0584, e-mail support(5)biocad.com Catalyst/Hypo for building molecular models, systematic conformational searching, and statistical fitting of 3D structural features to bioactivities. Phar-macophoric hypotheses can be used to search for matches in databases of 3D structures. Catalyst/Info for managing databases of ID, 2D, and 3D data. Silicon Graphics and networked Macintosh and PCs. 

The molecular modelling approach, taking into account the pyruvate—cinchona alkaloid interaction and the steric constraints imposed by the adsorption on the platinum surface, leads to a reasonable explanation for the enantio-differentiation of this system. Although the prediction of the complex formed between the methyl pyruvate and the cinchona modifiers have been made for an ideal case (solvent effects and a quantum description of the interaction with the platinum surface atoms were not considered), this approach proved to be very helpful in the search of new modifiers. The search strategy, which included a systematic reduction of the cinchona alkaloid structure to the essential functional parts and validation of the steric constraints imposed to the interaction complex between modifier and methyl pyruvate by means of molecular modelling, indicated that simple chiral aminoalcohols should be promising substitutes for cinchona alkaloid modifiers. Using the Sharpless symmetric dihydroxylation as a key step, a series of enantiomerically pure 2-hydroxy-2-aryl-ethylamines... 

G-Protein-coupled receptors do not lend themselves to analysis by either NMR or x-ray crystallography due to their structural dependence on an intact cell membrane. In our laboratories we pursued this valuable structural information by utilizing a combination of structural homology modeling, molecular dynamics, systematic conformational searching methods, and mutagenesis experiments. The combination of these techniques led to a proposed model of bradykinin bound to the agonist site on its receptor [41]. 

Molecular model-building (conformational search) methods fall into two general classes systematic and random. - Systematic methods search all possible combinations of torsional angles, whereas random methods usually involve a Monte Carlo (with Metropolis sampling ) or molecular dynamics trajectory. Both approaches attempt to search large areas of conformational space and eventually converge on the desired conformation or structure. Dis-... 

Random sampling, an approach in molecular modeling for conformational energy searching that relies on stochastic probing (Monte Carlo simulation). Different conformations are examined at random - in contrast to systematic searching - in order to explore the conformational space of a molecule. 

The search for satisfactory structures was initially carried out anafytically, with rather small use of simple molecular models. In the later stages, especially the systematic investigation of configurations corresponding to favoured orientations around the single bonds to the a-earbon atoms (Pauling A Corey 1951, ... 

Ketoprofen and 17 commonly used excipients were chosen as the probe systems for this study [81]. The molecular modelling has two parts prediction of crystal morphology followed by the prediction of binding energy of a probe molecule on the surfaces of the ketoprofen crystal. Three conformers for each of these excipients (probe molecules) were taken into consideration. For those excipient molecules which have more than one molecule in the asymmetric unit (e.g. sorbitol and a-lactose monohydrate), both the complete asymmetric unit as well as three conformers of a single molecule were considered as the probe conformations for the systematic search study. For those excipients that are polymers, a representative monomer unit was used as a probe molecule. 

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