Understanding the determinants of binding is essential to rational drug design. Not only must drugs bind tightly to their target(s), but they must also display tailored specificity. In this project, we use charge optimization, a previously published technique, to study molecular recognition. We vary the molecule's charge distribution to yield the most favorable binding free energy of the complex. By comparing the natural charge distribution to hypothetical optima, we hope to identify portions that, when altered, may allow a molecule to achieve tailored recognition.  We apply this technique to chronic myeloid leukemia drugs bound to Bcr-Abl oncoprotein. We hope to understand the differential binding of these drugs to the wild-type oncoprotein and mutant variants, supporting this analysis by extending it to a theoretical model system. By systematically varying parameters such as the size and shape of the model binding partners, we seek to gain insight into the determinants of binding.

Computational analysis of the electrostatic interaction between chronic myeloid leukemia drugs and Bcr-Abl kinase

245th National Meeting (2013)

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