Gerega Sebastien K, Downard Kevin M
School of Molecular and Microbial Biosciences, The University of Sydney, Sydney, NSW 2006, Australia.
Bioinformatics. 2006 Jul 15;22(14):1702-9. doi: 10.1093/bioinformatics/btl178. Epub 2006 May 5.
The design and implementation of a new algorithm, known as PROXIMO for protein oxidation interface modeller, is described to predict the structure of protein complexes using data generated in radical probe mass spectrometry (RP-MS) experiments. Photochemical radiolysis and discharge sources can be used to effect RP-MS in which hydroxyl radicals are formed directly from the bulk solvent on millisecond timescales and react with surface accessible residues in footprinting-like experiments. The algorithm utilizes a geometric surface fitting routine to predict likely structures for protein complexes. These structures are scored based on a correlation between the measured solvent accessibility of oxidizable residue side chains and oxidation shielding data obtained by RP-MS. The algorithm has been implemented to predict structures for the ribonuclease S-protein-peptide and calmodulin-melittin complexes using RP-MS data generated in this laboratory. The former is in close agreement with the high-resolution experimental structure available.
本文描述了一种名为PROXIMO（蛋白质氧化界面建模器）的新算法的设计与实现，该算法利用自由基探针质谱（RP-MS）实验中生成的数据来预测蛋白质复合物的结构。光化学辐射分解和放电源可用于实现RP-MS，在该过程中，羟基自由基在毫秒时间尺度上直接从大量溶剂中形成，并在类似足迹实验中与表面可及残基发生反应。该算法利用几何表面拟合程序来预测蛋白质复合物可能的结构。这些结构根据可氧化残基侧链的测量溶剂可及性与通过RP-MS获得的氧化屏蔽数据之间的相关性进行评分。该算法已被用于利用本实验室生成的RP-MS数据预测核糖核酸酶S-蛋白-肽和钙调蛋白-蜂毒素复合物的结构。前者与现有的高分辨率实验结构高度吻合。
