Understanding and predicting the specificity of small molecule protein interactions

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Many processes in living organisms are regulated through the interaction of small molecules (“ligands”) with proteins. Similarly, pharmaceutical agents are intended to stimulate or inhibit proteins. Understanding and predicting these interactions through computational methods (“docking”) is the purpose of this junior research group. The binding of a ligand to multiple proteins can either be the reason for high efficacy (in case of interaction with multiple diseaserelevant proteins) or severe side effects (in case of binding to undesired proteins). Thus, the main focus of the investigations will be on the specificity of the interactions. The goals of the research program are: (I) to generate a profile of the docking-predicted interactions between a molecule and multiple kinases and to identify agents against kinases implied in breast cancer; (II) to chart the binding pockets of kinases and G-protein-coupled receptors by docking small molecular probes and to suggest chemical modifications of existing ligands; and (III) to develop a fast method to estimate the conformational entropy of a rotatable bond in order to improve the prediction of ligand binding affinity.