Multi-Method Approaches for the Study of Complex Protein Interactions

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Just prior to this reporting period we have released and documented the global multi-method analysis (GMMA) software SEDPHAT, which offers a variety of models and specific statistical functions for the analysis of multi-component interactions in a multi-method approach. This has allowed us to shift our main focus from the development of GMMA to the search for model applications, as described in a separate project, and to further extend the flexibility of GMMA. In order to disseminate this tool and facilitate its application by colleagues, we have held workshops at NIH and in Japan, Germany, and Brazil. This has generated positive feedback and software improvements. Further, we have started to experimentally explore the potential for extending the global analysis to homo-oligomerization processes measured by isothermal titration microcalorimetry (ITC). Homo-oligomerization studies by ITC have been scarcely described in the literature, with typically small observable reaction enthalpies limiting wide-spread applications. Initial results are encouraging that, in conjunction with the new thermogram integration routines we developed recently, global analysis techniques will make this category of interactions better accessible. Finally, we have started to develop initial programming structures for the future extension of the GMMA approach to allow hierarchies of models to be fit side-by-side to experimental data utilizing different molecules.