COMPUTATIONAL DESIGN OF HAPTENS TO DESTROY COCAINE

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The ultimate goal of this research is to use the synergy between theory and experiment to design a molecule that will successfully induce catalytic antibodies having greater than 100,000-fold rate enhancement for the hydrolysis of cocaine. The results of quantum mechanical calculations will be used to refine the design of molecules, known as haptens that induce antibodies. My collaborator, Dr. Donald Landry, at the Columbia University College of Physicians and Surgeons, will synthesize the designed haptens and test their ability to generate catalytic antibodies. We will begin by identifying the appropriate level of theory needed to accurately model the available structural and kinetic data. We will then use the identified approach to model the intramolecular hydrolysis of cocaine. By comparing the molecular electrostatic potential (MEP) of the transition state with MEPs for different haptens, we will be able to identify the haptens that are closest to the actual transition state. The haptens most closely resembling the transition state structure will be used to generate catalytic antibodies. Correlating antibody catalytic efficiency with quantum mechanical predictions will identify the key insights obtainable from quantum chemistry, and enhance our understanding of how to generate the most efficient catalytic antibodies. Understanding how to elicit the most efficient catalytic antibodies would have wide- ranging implications for the scientific community. This project will increase our understanding of the potential for catalytic antibodies to be used for the treatment of drug addition.