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There are many aspects of a core laboratory that need to come together to create an environment for generating high-quality, quantitative molecular interactions data. Some of these aspects include having access to ample supplies of well-characterized, high-quality proteins (and other biomolecules). What biophysical characterization studies should be done with proteins and other biomolecules to understand the quality of the reagents prior to launching a detailed molecular interactions study? Should multiple molecular constructs of the proteins be created in advance to enable a more optimal experimental strategy for addressing the molecular interactions study? Should more than one “orthogonal” molecular interactions technology be used for a given interaction of interest? The focus of this presentation will be on outlining some guidelines for answering these types of questions.