Previous studies in our laboratory have shown that IGF-1R physically interacts with FAK to provide survival signals in human pancreatic cancer cells [34]. Further understanding of this mechanism may provide novel targets for drug treatment of pancreatic cancer. In the present study, using pull-downs with purified protein fragments, we demonstrate direct binding of a 116 amino
PluriSIn 1 fragment of the amino terminus of FAK with the intracellular domain of IGF-1R. Subsequently, computational molecular modeling was performed to predict the configuration of the binding between the amino terminus fragment of FAK and IGF-1R. Based on this information, small
molecules were screened by high performance computing, using van der Waals charges and electrostatic interactions, for binding to FAK in the pocket of interaction between FAK and IGF-1R. A representative small molecule was selected and shown to disrupt binding of FAK and IGF-1R. This information will be utilized to select additional molecules that disrupt FAK and IGF-1R signaling and function by disrupting their protein–protein interactions.
