Mapping the role of cofactors in the conformation of proteins using spectroscopy coupled with ion mobility mass spectrometry -summary to follow

我们获得了资金，以适应商业上可用的Synapt G2S HD MS(BBSRC BB/L002655/1)与Waters公司合作。这台仪器的核心是离子迁移率池，IM-MS测量在这台仪器中是可能的，就像任何Synapt质谱仪，但唯一的是，我们能够捕获离子的构象选择，以允许在所谓的‘照片SRIG’(叠环离子指南)的光学测量。这种光学测量可以采取几种形式，包括红外光谱、UV/VIS光谱，这将提供辅因子和辅酶的结构分析、光解离来对蛋白质进行排序以及荧光来探测全球构象。分子力学计算将产生与实验确定的结构相比较的结构。这个学生将使用这个新的仪器，通过对蛋白质的辅因子、载脂蛋白和全息形式进行测量，来检验辅因子对蛋白质构象的作用。学生将接受生物质谱学、光学方法和分子力学方面的培训。他们将借调到Waters开发软件，以最好地解释来自该仪器的数据。这一尖端的跨学科科学项目是世界领先的，将培养这名学生的一套技能，在学术界和工业界都是非常可取的。

We obtained funding to adapt a commercially available Synapt G2S HD MS (BBSRC BB/L002655/1) in collaboration with Waters Corp. The heart of this instrument is the ion mobility cell, IM-MS measurements are possible in this instrument, as for any Synapt mass spectrometer, but uniquely we are able to trap ions that have been conformer selected, to allow optical measurements in a so called 'photo SRIG' (stacked ring ion guide). Such optical measurements can take several forms, including IR-spectroscopy, UV/Vis-spectroscopy, which will provide structural analysis of co-factors and coenzymes, photo-dissociation to sequence the proteins as well as fluorescence to probe global conformations. Molecular mechanics calculations will generate structures to compare with those determined experimentally. This student will use this novel instrument to examine the role of cofactors on the conformations of proteins, by making measurements on the cofactor alone, the apo and the holo form of the protein. The student will be trained in biological mass spectrometry, in optical methods and in molecular mechanics. They will spend a secondment at Waters developing software to best interpret the data from this instrument. This cutting edge interdisciplinary science program is world leading and will train this student with a set of skills highly desirable both in academia and in industry.