This project is designed to """"""""build"""""""" a model for the cocaine recognition site using x-ray crystal structures, charge density studies and molecular modelling techniques. The first part of this study is designed to """"""""map"""""""" the three-dimensional structure and electronic character of (-)-cocaine and (-)-norcocaine. The mapping will not only include the overall geometry but will also be done with respect to the net atomic charges, electrostatic potentials, electric field gradients and intermolecular interaction energies. To calculate these quantities, carefully measured experimental x-ray data will be collected to accurately determine the electronic structure of (-)-cocaine and (-)- norcocaine. Routine x-ray crystal structures of several derivatives of cocaine will be completed in order to determine the three-dimensional structures and conformations of these molecules. This information in conjunction with the electronic structure of (-)-cocaine and (-)-norcocaine will be used to model the cocaine recognition site. This will give us a clearer understanding of the charge distribution and structural requirements for drug binding and action that occur at this site. Molecular modeling techniques will be used to """"""""build"""""""" a computer model of the cocaine recognition site. Results from the experimental charge density studies of (-)-cocaine and (-)-nor-cocaine, x-ray crystal structures of cocaine derivatives and other low energy structural conformations obtained through molecular mechanics will be used to """"""""build"""""""" the model.
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