Multi-Method Approaches for the Study of Complex Protein Interactions

就在本报告所述期间之前，我们发布并记录了全球多方法分析（GMMA）软件SEDPHAT，该软件提供了多种模型和特定的统计功能，用于以多方法方法分析多组分相互作用。 这使我们能够将我们的主要重点从开发GMMA转移到搜索模型应用程序，如在一个单独的项目中所述，并进一步扩展GMMA的灵活性。 为了传播这一工具并促进同事们的应用，我们在美国国立卫生研究院以及日本、德国和巴西举办了讲习班。 这产生了积极的反馈和软件改进。 此外，我们已经开始实验探索的潜力，扩大全球分析的均聚过程中测量的等温滴定微量热法（ITC）。 ITC的均聚研究在文献中几乎没有描述，通常可观察到的小反应范围限制了广泛的应用。 初步结果是令人鼓舞的，结合我们最近开发的新的热谱图集成例程，全球分析技术将使这一类的相互作用更好地访问。 最后，我们已经开始为GMMA方法的未来扩展开发初始编程结构，以允许模型的层次结构与利用不同分子的实验数据并排拟合。

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.