ISSN:
0192-8651
Keywords:
Computational Chemistry and Molecular Modeling
;
Biochemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
,
Computer Science
Notes:
A conformational study of cocaine and its three diastereomers, pseudococaine, allococaine, and allopseu-dococaine was carried out using molecular mechanics and quantum mechanical semiempirical techniques. Molecular dynamics simulations were performed at high temperature to scan their conformational space. Additional molecular dynamics at 312 K were used to explore the conformational flexibility of the compounds around the minimum energy conformation at physiologically relevant temperatures. The AM1 technique was used to refine the description of the minimum energy structures obtained with the molecular mechanics technique and to compute the electronic properties of cocaine and its diastereoisomers. Comparison of the results obtained with previous NMR and X-ray structural data was carried out. The structural information obtained was then used to discuss some aspects of the pharmacology of cocaine and other compounds that bind at the site recognized by it on the dopamine transporter.
Additional Material:
5 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jcc.540110915
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